
Citation: | Juan Zhou, Yiran Xu, Luyao Wang, Yu Cong, Ke Huang, Xinxing Pan, Guangquan Liu, Wenqu Li, Chenchen Dai, Pengfei Xu, Xuemei Jia. LncRNA IDH1-AS1 sponges miR-518c-5p to suppress proliferation of epithelial ovarian cancer cell by targeting RMB47[J]. The Journal of Biomedical Research, 2024, 38(1): 51-65. DOI: 10.7555/JBR.37.20230097 |
Long noncoding RNA (lncRNA) IDH1 antisense RNA 1 (IDH1-AS1) is involved in the progression of multiple cancers, but its role in epithelial ovarian cancer (EOC) is unknown. Therefore, we investigated the expression levels of IDH1-AS1 in EOC cells and normal ovarian epithelial cells by quantitative real-time PCR (qPCR). We first evaluated the effects of IDH1-AS1 on the proliferation, migration, and invasion of EOC cells through cell counting kit-8, colony formation, EdU, transwell, wound-healing, and xenograft assays. We then explored the downstream targets of IDH1-AS1 and verified the results by a dual-luciferase reporter, qPCR, rescue experiments, and Western blotting. We found that the expression levels of IDH1-AS1 were lower in EOC cells than in normal ovarian epithelial cells. High IDH1-AS1 expression of EOC patients from the Gene Expression Profiling Interactive Analysis database indicated a favorable prognosis, because IDH1-AS1 inhibited cell proliferation and xenograft tumor growth of EOC. IDH1-AS1 sponged miR-518c-5p whose overexpression promoted EOC cell proliferation. The miR-518c-5p mimic also reversed the proliferation-inhibiting effect induced by IDH1-AS1 overexpression. Furthermore, we found that RNA binding motif protein 47 (RBM47) was the downstream target of miR-518c-5p, that upregulation of RBM47 inhibited EOC cell proliferation, and that RBM47 overexpressing plasmid counteracted the proliferation-promoting effect caused by the IDH1-AS1 knockdown. Taken together, IDH1-AS1 may suppress EOC cell proliferation and tumor growth via the miR-518c-5p/RBM47 axis.
As an official paradigm for regulatory approval, the clinical assessment of pharmaceutical products is principally based on comprehensive evidence of efficacy and safety that can be substantially affected by immune-mediated side effects. Historically, immunogenicity-induced adverse reactions represent only a minimal portion of the drug-associated toxic profiles because of their rare incidence[1–2]. However, in the contemporary therapeutic landscape, concerns over untoward immune effects escalate, posing a significant challenge to medical practice and pharmaceutical development, especially with the advent of biological medicine characterized by their complex structures, that offer unique benefits in addressing unmet clinical needs[2–3]. In this scenario, it has been revealed that peptide/protein formulations can be antigenic, prompting the host immune system to generate anti-drug antibodies (ADAs) during patient treatment courses[3]. Moreover, antibody/cell-based medications exert their therapeutic effectiveness frequently through modulating the human immune system, which may simultaneously raise the possibility of immune-mediated untoward reaction[4–5].
It is increasingly recognized that human immune responses to pharmaceutical products have the potential to affect clinical pharmacodynamics, pharmacokinetics, efficacy, and safety in the treated patients[3]. Additionally, the presentation of immune-related adverse events (irAEs) varies considerably in terms of severity grades, including the manifestations such as rash, fever, organ damage, anaphylaxis, etc.[1,3,6]. To date, while having inspiring the development of numerous novel innovative medications, the interdisciplinary breakthroughs in biomedical sciences in recent years have significantly contributed to a better understanding of the cellular and molecular mechanisms behind drug immunity-driven adverse events[3,6]. In this context, official guidelines regarding the assessment of immunogenicity risks, as a part of toxicology reports, have recently been announced by the major regulatory agencies for large molecular pharmaceutical products, such as therapeutic proteins and heparin formulations, before approval for human use[3–4,7].
While novel categories of medications, such as RNA formulations and viral vector-bearing agents, increasingly enter the landscape of the medical market, unwanted immunogenicity is continuously evolving to face clinical practice, pharmaceuticals, and regulatory assessment[4,8]. Moreover, along with real-world data accumulated through post-marketing surveillance, the emerging aberrant immunity-linked adverse events need to be timely monitored for certain existing drugs[9]. Therefore, the current study presents an updated profile of untoward immune effects for major representative types of biomedical products, with the pathogenesis mechanisms to inspire pharmaceutical mitigation (Fig. 1).
The accumulation of knowledge regarding immune-mediated adverse reactions began with the understanding of the drug allergic phenotype triggered by low molecular weight medications, such as penicillin and sulfonamides[1,10]. It was hypothesized that these drugs became immunogenic to stimulate a host response by binding to serum proteins according to the hapten theory or by modifying the surface receptors of immune cells. The underlying pathogenesis pathways involving immunoglobulin E (IgE), IgG, IgM, drug-antibody complexes, and T cells, have led to various types of allergic events, such as anaphylaxis and delayed hypersensitivity reactions in the clinic[1,6]. While the medical presentation of chemical drug allergy are highly heterogeneous from skin lesions to organ damages, the list of etiologic compounds has continuously been extending to involve viral and kinase inhibitors among other emerging agents in recent years[1,6,11]. For instance, ibrutinib and idelalisib were sometimes observed to induce immune pathology-associated interstitial nephritis and pneumonitis, respectively[11–12]. Fresh insights into pathogenesis have revealed a link between specific human leukocyte antigen genes and differential chemical compounds. These antigen genes may serve as biomarkers in addition to skin tests to predict clinical risks of immunogenicity. Intriguingly, while cluster of differentiation 4 (CD4)+ T lymphocytes play a role in initiating drug-induced immunogenicity, CD8+ T cells contribute to the inflammatory organ pathology[6,13–14]. In medical practice, the mainstream approach for circumventing the challenge is to avoid the allergic agents but instead take alternative drugs without cross-reactivity[1,10]. On the other hand, from a pharmaceutical consideration, it has been proposed that the improved quality control of therapeutic products, such as the diminished antigenic epimers or allergy-linked structural elements in antibiotic development and manufacturing, helps down-regulate the interaction with IgE and can mitigate risks of drug immunogenicity[15–16].
Traditionally, therapeutic peptides represent the purified or recombinant versions of endogenous proteins that have important physiological activities and are normally circulating at low concentrations in the human body, including hormones, growth factors, clotting molecules, etc.[3,17]. Nonetheless, studies have shown that repeated injections of peptide medications over a long term can break immune tolerance to these self-antigens and thus induce specific lymphocyte activation with an elevated ADA[17–18]. In this sense, insulin antibodies (IAs) have been identified in diabetic patients for regular insulin treatments, and are associated with exogenous insulin antibody syndrome (EIAS) that is characterized by insulin resistance with hyperglycemia or hypoglycemia. Namely, the IAs with a low affinity/high capacity result in a postprandial hyperglycemia and a nocturnal hypoglycemia, meanwhile the IAs with a high affinity/low capacity induce EIAS with a severe insulin resistance[19]. Likewise, recombinant human erythropoietin (EPO) serves as an outstanding therapeutic peptide medicine for patients with low hemoglobin caused by certain serious illnesses, such as chronic renal disease and cancer. However, a long-term application of exogenous EPO may activate specific T cells, and thus stimulate the neutralizing ADAs that cross-react with endogenous EPO, leading to pure red cell aplasia consequently[20]. While the biological medication with recombinant factor Ⅷ confers a specific efficacy for the patients with hemophilia A, the neutralizing antibodies were stimulated in 20%–30% of the treated patients, thus resulting in the replacement therapy inefficient and even increasing mortality[21]. In terms of mitigating measures for the above-mentioned peptide drugs and beyond, one possibility is to stop the antigenic agents, shifting to alternative medical options if available in the clinic[3]. Regarding pharmaceutical optimization in parallel, it has been insightfully explored to de-immunize the therapeutic proteins through advanced formulations, post-translational modifications, or/and a selective point mutation strategy to remove those crucial sites binding to human leukocyte antigen in the sequence of amino acid residues with preservation of due biologic effects[18,20–21].
The success of targeted therapy driven by antibody technology has revolutionized clinical management in numerous aspects[5]. However, it is also recognized that antibody therapy may raise the morbidity of unwanted immune response-mediated side effects because of the immunity-modulating nature of antibody function and the potential antigenic activity of exogenous immunoglobulins that are characterized by a high molecular weight as well as a complex structure[3–4]. Therefore, the ADAs have been identified in up to 60% of autoimmune patients on the treatment of antibodies against tumor necrosis factor-α (TNF-α), including adalimumab, and these ADAs were largely neutralized[22–23]. Consequently, the anti-TNF-α inhibitor ADAs led to the reduced efficacious outcomes and higher rates of relevant side effects in the clinic[23]. On the other hand, anti-cancer immunotherapy of blocking immune checkpoint signaling frequently induces a wide spectrum of irAEs, ranging from skin rash to numerous organ lesions, including life-threatening myocarditis[24]. In this context, the toxicity of immune checkpoint inhibitors (ICIs) is mediated through an array of comprehensive mechanisms, including the elevated inflammatory cytokines, up-regulated auto-antibodies, and high activities of T cells against tumor and normal tissue antigens[25]. While autoimmunity signs of relevant organ pathology resulting from ICIs need to be mindfully monitored, medical management of these irAEs varies according to individual clinical grades[24,26]. Of note, the antibodies against the programmed cell death 1 (PD-1) receptor and its ligand (programmed death ligand 1, PD-L1) cause a lower incidence of any grade irAEs than the antibodies against cytotoxic T-lymphocyte antigen-4 (CTLA-4) do[9,24]. Intriguingly, whereas the mechanisms behind various mucocutaneous lesions upon treatment with differential anti-epithelial growth factor receptor (EGFR) are yet to be elucidated, a cellular immunity-based pathogenesis has been proposed[27]. As such, to reduce immune network-associated adverse events of the antibody therapy, examining the genetic background of individual patients proves clinically beneficial. For the interest of pharmaceutic research and development to diminish the immunotoxicity, the antibody structure-optimizing strategy comprises full human/humanization and removal of T-cell epitopes through computational prediction and protein engineering[3,27–28].
Over the past two decades, the biomedical landscape has been highlighted by the dramatic emergence of cellular therapy products, such as adaptive immune cells and stem cells, addressing unmet clinical needs of life-threatening illnesses[4–5]. In parallel, it is worth noting that the clinical application of these emerging biological products also comes with a high morbidity of irAEs because of bearing numerous cellular antigens and their potentially comprehensive immune mechanisms of action[5,9]. For example, chimeric antigen receptor T (CAR-T) cell therapy has achieved curative success in treating certain types of refractory hematological malignancies[4]. Unfortunately, the CAR-T cell approach may simultaneously cause a unique profile of severe adverse events upon activating potent immune cells, with cytokine-release syndrome and CAR-T cell-associated encephalopathy, posing major challenges for clinical practice[5,12,29]. To deal with these problems, while corticosteroids and the inflammatory cytokine-neutralizing antibodies appear to be helpful for mitigating the toxic effects, optimized CAR-T cells through an improved engineering gene vector of the third generation have been shown to reduce the irAEs without compromising anti-cancer efficacy[30–31]. Beyond the hematological indications, the stem cell therapy strategy has been demonstrated to confer clinical benefits for several parenchymal cell damage-caused organ lesions without efficacious treatment, such as myocardial infarction and spinal cord injury[30]. Accordingly, to address the immunogenicity issues in those contexts, immune-privileged approaches have been in progress, including mesenchymal stromal cells, autologous induced pluripotent stem cells, and the knockout of major histocompatibility complex (MHC) through gene editing technology[32–33].
Heparin-derived medications have significantly contributed to the management of thrombotic pathology in a wide variety of clinical conditions[34]. Meanwhile, concerning the adverse effects of heparin compounds, an immunogenicity-mediated complication termed heparin-induced thrombocytopenia (HIT) should not be ignored[35]. Of note, HIT is characterized by distintive features, including platelet factor 4 (PF4) involvement, platelet activation, and elevated antibodies. Accordingly, there is a consensus that the immunogenicity tests for heparin-associated products need to characterize the molecular complex formed by PF4 binding with heparin polysaccharides and others[7,36]. In clinical settings, an array of associated risk factors have been observed, including long-term injection of heparin agents, concomitant autoimmune disorders, and surgical inflammation[37]. Regarding the source and structure of active pharmaceutical ingredients, bovine heparin appeared to have a higher incidence of HIT than porcine-derived heparin compounds, whereas unfractionated heparin (UFH) was speculated to induce more HIT events than low molecular weight heparin (LMWH) formulations, such as dalteparin and enoxaparin[36–37]. A plausible explanation is that LMWH agents have lower molecular weights, compared with UFH, thus being less likely to interact with immune cells and particularly circulating white blood cells[34,38]. Moreover, as one of the novel synthetic heparin-like compounds, fondaparinux emerges as a better therapeutic option for indicated patients at HIT risk induced by UFH or LMWH immunogenicity[39].
In recent years, there has been a remarkable advancement in gene function modulation at the nucleic acid level, which is dramatically translated from basic science into beside in the clinic, such as RNA-based approaches[40–41]. Impressively, mRNA vaccines against coronavirus 2019 (COVID-19) have been developed as an outstanding innovative medication to confer a prophylactic efficacy with a therapeutic benefit in alleviating clinical severity of the disease[41–42]. Nonetheless, it has also been noted that mRNA vaccines can induce untoward immunogenicity that leads to rare adverse events. In this regard, the emerging myocarditis and immune thrombocytopenia with subcutaneous hemorrhage upon the vaccination may require corticosteroid hormone treatment[43–44]. Accordingly, to mitigate the immuno-toxicity of mRNA agents, improvement of the delivering techniques has been proposed, in addition to nucleotide sequence modifications, such as 5′-end capping, and the selected point methylation[42,45].
At the DNA level, the recombinant adeno-associated virus (AAV) vector system has emerged as the most popular platform for delivering gene therapy[46]. To date, several AAV-based bio-pharmaceutical products have been approved to enter the medical market to address certain unmet clinical needs, particularly single gene defect-caused diseases, such as hereditary lipoprotein lipase deficiency and spinal muscular atrophy type 1[46–47]. Unfortunately, anti-AAV antibodies are identified in the majority of human populations, even prior to the treatment initiation with an increase to higher levels afterward[4,46]. On the other hand, it is noted that cellular immunity involving CD4+ and CD8+ T lymphocytes is activated upon the AAV gene therapy, leading to hepatocyte damage, liver failure, and systemic inflammation in worse scenarios[47–48]. Moreover, COVID-19 vaccines based on adenovirus vectors have been associated with a rare adverse event of immune thrombotic thrombocytopenia[49–50]. To address these complicated immunogenicity issues, ongoing approaches focus on optimizing the engineering of the capsid variants to evade pre-existing ADA[45], and improving tissue-selective gene delivery to avoid off-target organ involvement[47,51]. Of note, there is an escalating interest in applying AAV gene therapy to treat certain genetic disorders of the eyes, because the immune-privileged location and minor dosing of viral vectors needed for the therapeutic purpose therein[46,52].
Addressing untoward immune effects of medications has been a focus for over half a century, and this effort has intensified in recent years with the evolving therapeutic landscape and the emergence of novel biological products (Table 1). As extremely rare scenarios, allergic events to small chemical compounds are currently stimulating the development of contemporary targeted pharmaceutical agents[12]. It should be noted that in vitro synthetic or genetic engineering-expressed peptide/protein products of human sequences have substantially minimized the immunogenicity, compared with those isolated from animal sources. In contrast, checkpoint-inhibiting antibodies are associated with a remarkably higher incidence of immune-mediated adverse reactions[24,27]. Whereas certain autogenic cell manipulation-based therapies have achieved unique clinical successes, allogenic cell approaches often encounter challenges with immune rejection[29,31]. Interestingly, although the advanced molecular modifications and delivering materials have dramatically diminished the immunotoxicity of gene medications, few emerging biological agent-induced severe adverse events are yet to be deciphered[43–44]. Therefore, according to the relevant regulatory guidelines, immunogenicity risks of biotherapeutic products must be assessed throughout their whole life cycles[3–4,53].
Categories | Examples | Pathogenesis | Mitigation | References |
Penicillin | Hapten model, ADA/IgE, and histamine release | Structural modification and epimer removing | ||
Small molecule | Sulfonamide | [1,15–16] | ||
NSAIDS | ||||
Insulin | Breaking immune tolerance, and ADA/IgG | Human sequence synthesis/recombination and structural optimization | [18,20–21] | |
Peptide | Erythropoietin | |||
Factor Ⅷ | ||||
Adalimumab | ADA/IgG, and T-cell activation | Human sequence deimmunization and target differentiation | [3,27–28] | |
Antibody | Nivolumab | |||
Pembrolizumab | ||||
Cellular therapy | CAR-T | T-cell activation Immune rejection | Autogenic source and allogenic MHC deleting | [30–31] |
Stem cell | [32–33] | |||
Heparin | UFH | PF4-heparin complex, and ADA/HIT IgG | Raw material control and processing optimization | [37–39] |
LMWH | ||||
Gene medicine | mRNA agent | ADA/IgG/IgE, T-cell activation, and PF4 | Site-specific modification and delivering optimization | [45–46,51] |
Viral formulation | ||||
Abbreviations: NSAIDS, non-steroidal anti-inflammatory drugs; ADA, anti-drug antibody; CAR-T, chimeric antigens receptor-T cell; MHC, major histocompatibility complex; UFH, unfractionated heparin; LMWH, low molecular weight heparin; PF4, platelet factor 4; HIT, heparin-induced thrombocytopenia. |
Looking forward, while ADA, particularly with its neutralizing activity, has been defined as a key parameter to predict potential risks of unwanted immunogenicity, a more comprehensive dissection of the relevant immune modulating network is necessary for the upcoming wave of biological agents[54]. In the field of cancer immunotherapy, clinical practice is witnessing an intriguing dynamic, where irAEs may be associated with therapeutic effectiveness[55], which conceivably inspire pharmacovigilance services to more thoughtfully evaluate benefits over risks[24]. Moreover, advanced technique platforms are innovatively developed to mitigate the emerging immune-mediated toxicities of new-generation biological medications, such as the MHC gene deletion for universal CAR-T cells[56] and the sequence site-specific modifications for mRNA vaccines[45]. Hence, taking advantages of the cutting-edge scientific progress, extraordinary protein/cell/gene-based products with breakthrough efficacy are emerging to address unmet medical needs, and may simultaneously be complicated with novel untoward immune effects; for the latter challenges, relevant mitigating measures are evolving upon insights into advanced pharmaceutic processing arts and human host biology[3,57].
We acknowledge and appreciate our institutional colleagues for their experimental technical support.
CLC number: R73-3, Document code: A
The authors reported no conflict of interests.
[1] |
Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023[J]. CA Cancer J Clin, 2023, 73(1): 17–48. doi: 10.3322/caac.21763
|
[2] |
Wang M, Zhang J, Wu Y. Tumor metabolism rewiring in epithelial ovarian cancer[J]. J Ovarian Res, 2023, 16(1): 108. doi: 10.1186/s13048-023-01196-0
|
[3] |
Kuroki L, Guntupalli SR. Treatment of epithelial ovarian cancer[J]. BMJ, 2020, 371: m3773. doi: 10.1136/bmj.m3773
|
[4] |
Salamini-Montemurri M, Lamas-Maceiras M, Lorenzo-Catoira L, et al. Identification of lncRNAs deregulated in epithelial ovarian cancer based on a gene expression profiling meta-analysis[J]. Int J Mol Sci, 2023, 24(13): 10798. doi: 10.3390/ijms241310798
|
[5] |
Zhao S, Zhang X, Chen S, et al. Natural antisense transcripts in the biological hallmarks of cancer: powerful regulators hidden in the dark[J]. J Exp Clin Cancer Res, 2020, 39(1): 187. doi: 10.1186/s13046-020-01700-0
|
[6] |
Xu F, Huang M, Chen Q, et al. LncRNA HIF1A-AS1 promotes gemcitabine resistance of pancreatic cancer by enhancing glycolysis through modulating the AKT/YB1/HIF1α pathway[J]. Cancer Res, 2021, 81(22): 5678–5691. doi: 10.1158/0008-5472.CAN-21-0281
|
[7] |
Yang L, Chen Y, Liu N, et al. Low expression of TRAF3IP2-AS1 promotes progression of NONO-TFE3 translocation renal cell carcinoma by stimulating N6-methyladenosine of PARP1 mRNA and downregulating PTEN[J]. J Hematol Oncol, 2021, 14(1): 46. doi: 10.1186/s13045-021-01059-5
|
[8] |
Liu Y, Zhang P, Wu Q, et al. Long non-coding RNA NR2F1-AS1 induces breast cancer lung metastatic dormancy by regulating NR2F1 and ΔNp63[J]. Nat Commun, 2021, 12(1): 5232. doi: 10.1038/s41467-021-25552-0
|
[9] |
Xiang S, Gu H, Jin L, et al. LncRNA IDH1-AS1 links the functions of c-Myc and HIF1α via IDH1 to regulate the Warburg effect[J]. Proc Natl Acad Sci U S A, 2018, 115(7): E1465–E1474. doi: 10.1073/pnas.1711257115
|
[10] |
Zhang N, Li Z, Bai F, et al. PAX5-induced upregulation of IDH1-AS1 promotes tumor growth in prostate cancer by regulating ATG5-mediated autophagy[J]. Cell Death Dis, 2019, 10(10): 734. doi: 10.1038/s41419-019-1932-3
|
[11] |
Wang J, Quan Y, Lv J, et al. LncRNA IDH1-AS1 suppresses cell proliferation and tumor growth in glioma[J]. Biochem Cell Biol, 2020, 98(5): 556–564. doi: 10.1139/bcb-2019-0465
|
[12] |
Braga EA, Fridman MV, Moscovtsev AA, et al. LncRNAs in ovarian cancer progression, metastasis, and main pathways: ceRNA and alternative mechanisms[J]. Int J Mol Sci, 2020, 21(22): 8855. doi: 10.3390/ijms21228855
|
[13] |
Klar M, Hasenburg A, Hasanov M, et al. Prognostic factors in young ovarian cancer patients: An analysis of four prospective phase III intergroup trials of the AGO Study Group, GINECO and NSGO[J]. Eur J Cancer, 2016, 66: 114–124. doi: 10.1016/j.ejca.2016.07.014
|
[14] |
Chang LC, Huang CF, Lai MS, et al. Prognostic factors in epithelial ovarian cancer: a population-based study[J]. PLoS One, 2018, 13(3): e0194993. doi: 10.1371/journal.pone.0194993
|
[15] |
Rosendahl M, Høgdall CK, Mosgaard BJ. Restaging and survival analysis of 4036 ovarian cancer patients according to the 2013 FIGO classification for ovarian, fallopian tube, and primary peritoneal cancer[J]. Int J Gynecol Cancer, 2016, 26(4): 680–687. doi: 10.1097/IGC.0000000000000675
|
[16] |
Peres LC, Cushing-Haugen KL, Köbel M, et al. Invasive epithelial ovarian cancer survival by histotype and disease stage[J]. J Natl Cancer Inst, 2019, 111(1): 60–68. doi: 10.1093/jnci/djy071
|
[17] |
Martinez A, Pomel C, Filleron T, et al. Prognostic relevance of celiac lymph node involvement in ovarian cancer[J]. Int J Gynecol Cancer, 2014, 24(1): 48–53. doi: 10.1097/IGC.0000000000000041
|
[18] |
Ataseven B, Grimm C, Harter P, et al. Prognostic value of lymph node ratio in patients with advanced epithelial ovarian cancer[J]. Gynecol Oncol, 2014, 135(3): 435–440. doi: 10.1016/j.ygyno.2014.10.003
|
[19] |
Wu S, Ding L, Xu H, et al. The long non-coding RNA IDH1-AS1 promotes prostate cancer progression by enhancing IDH1 enzyme activity[J]. Onco Targets Ther, 2020, 13: 7897–7906. doi: 10.2147/OTT.S251915
|
[20] |
Chen L. Linking long noncoding RNA localization and function[J]. Trends Biochem Sci, 2016, 41(9): 761–772. doi: 10.1016/j.tibs.2016.07.003
|
[21] |
Fernandes JCR, Acuña SM, Aoki JI, et al. Long non-coding RNAs in the regulation of gene expression: physiology and disease[J]. Non-Coding RNA, 2019, 5(1): 17. doi: 10.3390/ncrna5010017
|
[22] |
Fan Y, Wang L, Han X, et al. LncRNA ASB16-AS1 accelerates cellular process and chemoresistance of ovarian cancer cells by regulating GOLM1 expression via targeting miR-3918[J]. Biochem Biophys Res Commun, 2023, 675: 1–9. doi: 10.1016/j.bbrc.2023.06.068
|
[23] |
Su M, Huang P, Li Q. Long noncoding RNA SNHG6 promotes the malignant phenotypes of ovarian cancer cells via miR-543/YAP1 pathway[J]. Heliyon, 2023, 9(5): e16291. doi: 10.1016/j.heliyon.2023.e16291
|
[24] |
Li Y, Zhu X, Zhang C, et al. Long noncoding RNA FTX promotes epithelial-mesenchymal transition of epithelial ovarian cancer through modulating miR-7515/TPD52 and activating Met/Akt/mTOR[J]. Histol Histopathol, 2023, 9: 18620. doi: 10.14670/HH-18-620
|
[25] |
Flor I, Bullerdiek J. The dark side of a success story: microRNAs of the C19MC cluster in human tumours[J]. J Pathol, 2012, 227(3): 270–274. doi: 10.1002/path.4014
|
[26] |
Dyrskjøt L, Ostenfeld MS, Bramsen JB, et al. Genomic profiling of microRNAs in bladder cancer: miR-129 is associated with poor outcome and promotes cell death in vitro[J]. Cancer Res, 2009, 69(11): 4851–4860. doi: 10.1158/0008-5472.CAN-08-4043
|
[27] |
Zhao J, Yang J, Lin J, et al. Identification of miRNAs associated with tumorigenesis of retinoblastoma by miRNA microarray analysis[J]. Childs Nerv Syst, 2009, 25(1): 13–20. doi: 10.1007/s00381-008-0701-x
|
[28] |
Kinouchi M, Uchida D, Kuribayashi N, et al. Involvement of miR-518c-5p to growth and metastasis in oral cancer[J]. PLoS One, 2014, 9(12): e115936. doi: 10.1371/journal.pone.0115936
|
[29] |
He J, Han Z, Luo J, et al. Hsa_Circ_0007843 acts as a miR-518c-5p sponge to regulate the migration and invasion of colon cancer SW480 cells[J]. Front Genet, 2020, 11: 9. doi: 10.3389/fgene.2020.00009
|
[30] |
Fossat N, Radziewic T, Jones V, et al. Conditional restoration and inactivation of Rbm47 reveal its tissue-context requirement for viability and growth[J]. Genesis, 2016, 54(3): 115–122. doi: 10.1002/dvg.22920
|
[31] |
Radine C, Peters D, Reese A, et al. The RNA-binding protein RBM47 is a novel regulator of cell fate decisions by transcriptionally controlling the p53-p21-axis[J]. Cell Death Differ, 2020, 27(4): 1274–1285. doi: 10.1038/s41418-019-0414-6
|
[32] |
Sakurai T, Isogaya K, Sakai S, et al. RNA-binding motif protein 47 inhibits Nrf2 activity to suppress tumor growth in lung adenocarcinoma[J]. Oncogene, 2016, 35(38): 5000–5009. doi: 10.1038/onc.2016.35
|
[33] |
Guo T, You K, Chen X, et al. RBM47 inhibits hepatocellular carcinoma progression by targeting UPF1 as a DNA/RNA regulator[J]. Cell Death Discov, 2022, 8(1): 320. doi: 10.1038/s41420-022-01112-3
|
[34] |
Qin Y, Sun W, Wang Z, et al. RBM47/SNHG5/FOXO3 axis activates autophagy and inhibits cell proliferation in papillary thyroid carcinoma[J]. Cell Death Dis, 2022, 13(3): 270. doi: 10.1038/s41419-022-04728-6
|
[35] |
Shen D, Jiang Y, Li J, et al. The RNA-binding protein RBM47 inhibits non-small cell lung carcinoma metastasis through modulation of AXIN1 mRNA stability and Wnt/β-catentin signaling[J]. Surg Oncol, 2020, 34: 31–39. doi: 10.1016/j.suronc.2020.02.011
|
[1] | Izzatullo Ziyoyiddin o`g`li Abdullaev, Ulugbek Gapparjanovich Gayibov, Sirojiddin Zoirovich Omonturdiev, Sobirova Fotima Azamjonovna, Sabina Narimanovna Gayibova, Takhir Fatikhovich Aripov. Molecular pathways in cardiovascular disease under hypoxia: Mechanisms, biomarkers, and therapeutic targets[J]. The Journal of Biomedical Research. DOI: 10.7555/JBR.38.20240387 |
[2] | Chen Li, Kerui Wang, Xingfeng Mao, Xiuxiu Liu, Yingmei Lu. Upregulated inwardly rectifying K+ current-mediated hypoactivity of parvalbumin interneuron underlies autism-like deficits in Bod1-deficient mice[J]. The Journal of Biomedical Research. DOI: 10.7555/JBR.38.20240394 |
[3] | Siyun Zhou, Yan Li, Wenqing Sun, Dongyu Ma, Yi Liu, Demin Cheng, Guanru Li, Chunhui Ni. circPVT1 promotes silica-induced epithelial-mesenchymal transition by modulating the miR-497-5p/TCF3 axis[J]. The Journal of Biomedical Research, 2024, 38(2): 163-174. DOI: 10.7555/JBR.37.20220249 |
[4] | Dandan Zheng, Xiya Zhang, Jia Xu, Shuwen Chen, Bin Wang, Xiaoqin Yuan. LncRNA LINC01503 promotes angiogenesis in colorectal cancer by regulating VEGFA expression via miR-342-3p and HSP60 binding[J]. The Journal of Biomedical Research. DOI: 10.7555/JBR.38.20240190 |
[5] | Pei Tan, Mu Xu, Junjie Nie, Jian Qin, Xiangxiang Liu, Huiling Sun, Shukui Wang, Yuqin Pan. LncRNA SNHG16 promotes colorectal cancer proliferation by regulating ABCB1 expression through sponging miR-214-3p[J]. The Journal of Biomedical Research, 2022, 36(4): 231-241. DOI: 10.7555/JBR.36.20220049 |
[6] | Zhu Ping, Shan Xia, Liu Jinhui, Zhou Xin, Zhang Huo, Wang Tongshan, Wu Jianqing, Zhu Wei, Liu Ping. miR-3622b-5p regulates cisplatin resistance of human gastric cancer cell line by targeting BIRC5[J]. The Journal of Biomedical Research, 2019, 33(6): 382-390. DOI: 10.7555/JBR.33.20180078 |
[7] | Wang Jing, He Xuezhi, Lu Xiyi, Amin Karim Muhammad, Miao Dengshun, Zhang Erbao. A novel long non-coding RNA NFIA-AS1 is down-regulated in gastric cancer and inhibits proliferation of gastric cancer cells[J]. The Journal of Biomedical Research, 2019, 33(6): 371-381. DOI: 10.7555/JBR.33.20190015 |
[8] | Huanqiang Wang, Congying Yang, Siyuan Wang, Tian Wang, Jingling Han, Kai Wei, Fucun Liu, Jida Xu, Xianzhen Peng, Jianming Wang. Cell-free plasma hypermethylated CASZ1, CDH13 and ING2 are promising biomarkers of esophageal cancer[J]. The Journal of Biomedical Research, 2018, 32(6): 424-433. DOI: 10.7555/JBR.32.20170065 |
[9] | Yi Zhang, Jing Wu, Junya Liang, Xing Huang, Lei Xia, Dawei Ma, Xinyu Xu, Pingping Wu. Association of serum lipids and severity of epithelial ovarian cancer: an observational cohort study of 349 Chinese patients[J]. The Journal of Biomedical Research, 2018, 32(5): 336-342. DOI: 10.7555/JBR.32.20170096 |
[10] | Lihong Chen, Lianxiang Li, Feng Chen, Dalin He. Immunoexpression and prognostic role of p53 in different subtypes of epithelial ovarian carcinoma[J]. The Journal of Biomedical Research, 2012, 26(4): 274-277. DOI: 10.7555/JBR.26.20110103 |
Categories | Examples | Pathogenesis | Mitigation | References |
Penicillin | Hapten model, ADA/IgE, and histamine release | Structural modification and epimer removing | ||
Small molecule | Sulfonamide | [1,15–16] | ||
NSAIDS | ||||
Insulin | Breaking immune tolerance, and ADA/IgG | Human sequence synthesis/recombination and structural optimization | [18,20–21] | |
Peptide | Erythropoietin | |||
Factor Ⅷ | ||||
Adalimumab | ADA/IgG, and T-cell activation | Human sequence deimmunization and target differentiation | [3,27–28] | |
Antibody | Nivolumab | |||
Pembrolizumab | ||||
Cellular therapy | CAR-T | T-cell activation Immune rejection | Autogenic source and allogenic MHC deleting | [30–31] |
Stem cell | [32–33] | |||
Heparin | UFH | PF4-heparin complex, and ADA/HIT IgG | Raw material control and processing optimization | [37–39] |
LMWH | ||||
Gene medicine | mRNA agent | ADA/IgG/IgE, T-cell activation, and PF4 | Site-specific modification and delivering optimization | [45–46,51] |
Viral formulation | ||||
Abbreviations: NSAIDS, non-steroidal anti-inflammatory drugs; ADA, anti-drug antibody; CAR-T, chimeric antigens receptor-T cell; MHC, major histocompatibility complex; UFH, unfractionated heparin; LMWH, low molecular weight heparin; PF4, platelet factor 4; HIT, heparin-induced thrombocytopenia. |