Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla 34956, Istanbul, Turkey; Center of Excellence for Functional Surfaces and Interfaces (EFSUN), Faculty of Engineering and Natural Sciences, Sabanci University, Tuzla, Istanbul 34956, Turkey.
Life Sci. 2020 Sep 1;256:117973. doi: 10.1016/j.lfs.2020.117973. Epub 2020 Jun 20.
The resistance of cancer cells into chemotherapy has restricted the efficiency of anti-tumor drugs. Oxaliplatin (OX) being an anti-tumor agent/drug is extensively used in the treatment of various cancer diseases. However, its frequent application has led to chemoresistance. As a consequence, studies have focused in finding underlying molecular pathways involved in OX resistance. MicroRNAs (miRs) are short endogenous non-coding RNAs that are able to regulate vital biological mechanisms such as cell proliferation and cell growth. The abnormal expression of miRs occurs in pathological events, particularly cancer. In the present review, we describe the involvement of miRs in OX resistance and sensitivity. The miRs are able to induce the oncogene factors and mechanisms, resulting in stimulation OX chemoresistance. Also, onco-suppressor miRs can enhance the sensitivity of cancer cells into OX chemotherapy and trigger apoptosis and cell cycle arrest, leading to reduced viability and progression of cancer cells. MiRs can also enhance the efficacy of OX chemotherapy. It is worth mentioning that miRs affect various down-stream targets in OX resistance/sensitivity such as STAT3, TGF-β, ATG4B, FOXO1, LATS2, NF-κB and so on. By identification of these miRs and their upstream and down-stream mediators, further studies can focus on targeting them to sensitize cancer cells into OX chemotherapy and induce apoptotic cell death.
癌细胞对化疗的耐药性限制了抗肿瘤药物的疗效。奥沙利铂(OX)作为一种抗肿瘤药物/药物,被广泛用于治疗各种癌症疾病。然而,其频繁的应用导致了耐药性。因此,研究集中在寻找与 OX 耐药性相关的潜在分子途径。微小 RNA(miRs)是短的内源性非编码 RNA,能够调节细胞增殖和细胞生长等重要的生物学机制。miRs 的异常表达发生在病理事件中,特别是癌症。在本综述中,我们描述了 miRs 参与 OX 耐药性和敏感性。miRs 能够诱导癌基因因子和机制,从而刺激 OX 化疗耐药性。此外,癌基因抑制性 miRs 可以增强癌细胞对 OX 化疗的敏感性,并触发细胞凋亡和细胞周期停滞,导致癌细胞活力和进展减少。miRs 还可以增强 OX 化疗的疗效。值得一提的是,miRs 影响 OX 耐药性/敏感性中的各种下游靶标,如 STAT3、TGF-β、ATG4B、FOXO1、LATS2、NF-κB 等。通过鉴定这些 miRs 及其上游和下游介质,进一步的研究可以集中在靶向它们以增加癌细胞对 OX 化疗的敏感性并诱导细胞凋亡。