Yang Yubo, Dai Cuihong, Cai Zhipeng, Hou Aiju, Cheng Dayou, Wu Guanying, Li Jing, Cui Jie, Xu Dechang
IEEE Trans Nanobioscience. 2016 Mar;15(2):113-8. doi: 10.1109/TNB.2016.2539365. Epub 2016 Mar 23.
Chemotherapy is the main strategy in the treatment of cancer; however, the development of drug-resistance is the obstacle in long-term treatment of cervical cancer. Cisplatin is one of the most common drugs used in cancer therapy. Recently, accumulating evidence suggests that miRNAs are involved in various bioactivities in oncogenesis. It is not unexpected that miRNAs play a key role in acquiring of drug-resistance in the progression of tumor. In this study, we induced and maintained four levels of cisplatin-resistant HeLa cell lines (HeLa/CR1, HeLa/CR2, HeLa/CR3, and HeLa/CR4). According to the previous studies and existing evidence, we selected five miRNAs (miR-183, miR-182, miR-30a, miR-15b, and miR-16) and their potential target mRNAs as our research targets. The real-time RT-PCR was adopted to detect the relative expression of miRNAs and their mRNAs. The results show that miR-182 and miR-15b were up-regulated in resistant cell lines, while miR-30a was significantly down-regulated. At the same time, their targets are related to drug resistance. Compared to their parent HeLa cell line, the expression of selected miRNAs in resistant cell lines altered. The alteration suggests that HeLa cell drug resistance is associated with distinct miRNAs, which indicates that miRNAs may be one of the therapy targets in the treatment of cervical cancer by sensitizing cell to chemotherapy. We suggested a possible network diagram based on the existing theory and the preliminary results of candidate miRNAs and their targets in HeLa cells during development of drug resistance.
化疗是癌症治疗的主要策略；然而，耐药性的产生是宫颈癌长期治疗的障碍。顺铂是癌症治疗中最常用的药物之一。最近，越来越多的证据表明，微小RNA（miRNAs）参与肿瘤发生的各种生物活性。miRNAs在肿瘤进展中获得耐药性方面发挥关键作用并不意外。在本研究中，我们诱导并维持了四个水平的顺铂耐药HeLa细胞系（HeLa/CR1、HeLa/CR2、HeLa/CR3和HeLa/CR4）。根据先前的研究和现有证据，我们选择了五个miRNAs（miR-183、miR-182、miR-30a、miR-15b和miR-16）及其潜在的靶mRNA作为我们的研究靶点。采用实时逆转录聚合酶链反应（RT-PCR）检测miRNAs及其mRNA的相对表达。结果表明，miR-182和miR-15b在耐药细胞系中上调，而miR-30a显著下调。同时，它们的靶点与耐药性有关。与亲本HeLa细胞系相比，耐药细胞系中所选miRNAs的表达发生了改变。这种改变表明HeLa细胞耐药性与不同的miRNAs相关，这表明miRNAs可能是通过使细胞对化疗敏感来治疗宫颈癌的治疗靶点之一。我们根据现有理论以及HeLa细胞在耐药性发展过程中候选miRNAs及其靶点的初步结果提出了一个可能的网络图。
