Abstract：Objective To investigate the effects and molecular mechanisms of miR-139-5p on cisplatin sensitivity of nasopharyngeal carcinoma cisplatin-resistant cells.Methods The cultured nasopharyngeal carcinoma cisplatin (DDP) resistant cell line HNE1/DDP cells were divided into miR-139-5p group, negative control group, DDP group and blank control group.The miR-139-5p group was transfected with miR-139-5p mimics and the negative control group was transfected with negative control sequences. The DDP group and the blank control group were not treated. After transfection, 20 μmol/L DDP was added to the miR-139-5p group, negative control group, and DDP group. The blank control group was only given the medium, and the apoptosis rate of each group of HNE1/DDP cells was detected by single staining with propiodide (PI). The expression levels of phosphatidylinositid 3-kinase(PI3K), p-PI3K, protein kinase B(Akt), p-Akt and chemokine receptor 4(CXCR4) proteins in miR-139-5p group, negative control group and blank control group were detected by Western blot. The mRNA expression levels of CXCR4 in miR-139-5p group, negative control group and blank control group were detected by real-time quantitative PCR (RT-qPCR).Results The apoptosis rate detection of HNE1/DDP cells showed that the apoptosis rate of blank control group, DDP group, negative control group and miR-139-5p group were 6.26%±1.19%, 22.43%±3.88%, 23.87%±3.21% and 40.87±4.04%, respectively. The apoptosis rates of DDP group, negative control group and miR-139-5p group were significantly higher than that of the blank control group,and the apoptosis rate of miR-139-5p group was significantly higher than those of DDP group and negative control group. The difference was statistically significant (all P values＜0.05). Western blot analysis showed that the relative expression levels of p-Akt, p-PI3K, PI3K, and CXCR4 proteins in miR-139-5p group were significantly lower than those in blank control group and negative control group (all P values＜0.01) . The results of RT-qPCR showed that the mRNA expression level of CXCR4 in the miR-139-5p group was significantly lower than those in the blank control group and the negative control group, and the difference was statistically significant (all P values＜0.01).Conclusions Transfection of miR-139-5p can significantly increase the sensitivity of nasopharyngeal carcinoma cell line HNE1/DDP to cisplatin, which may be related to the inhibition of the expression of CXCR4 and the regulation of the activation of its downstream PI3K/Akt signaling pathway.
邵倩倩, 马莹晔, 李慧, 王晓敏, 张明洁, 陈德尚, 陆兆屹, 孟洁, 马士崟. MiR-139-5p通过靶向CXCR4/PI3K/Akt信号通路增强鼻咽癌顺铂耐药细胞对顺铂的敏感性[J]. 中华解剖与临床杂志, 2018, 23(2): 149-154.
Shao Qianqian, Ma Yingye, Li Hui, Wang Xiaoming, Zhang Mingjie, Chen Deshang, Lu Zhaoyi, Meng Jie, Ma Shiyin. Enhancing the sensitivity of nasopharyngeal carcinoma cells to cisplatin with MiR-139-5p by targeting CXCR4/PI3K/Akt signaling pathway. Chinese Journal of Anatomy and Clinics, 2018, 23(2): 149-154.
McDermott AL, Dutt SN, Watkinson JC. The aetiology of nasopharyngeal carcinoma[J]. Clin Otolaryngol Allied Sci, 2001, 26(2): 82-92. DOI: 10.1046/j.1365-2273.2001.00449.x
[2]
Chen QY, Wen YF, Guo L, et al. Concurrent chemoradiotherapy vs radiotherapy alone in stage Ⅱ nasopharyngeal carcinoma: phase Ⅲ randomized trial[J]. J Natl Cancer Inst, 2011, 103(23): 1761-1770. DOI:10.1093/jnci/djr432
[3]
Markopoulos GS, Roupakia E, Tokamani M, et al. A step-by-step microRNA guide to cancer development and metastasis[J]. Cell Oncol (Dordr), 2017, 40(4): 303-339. DOI:10.1007/s13402-017-0341-9
[4]
Shi L, Xu Z, Wu G, et al. Up-regulation of miR-146a increases the sensitivity of non-small cell lung cancer to DDP by downregulating cyclin J[J]. BMC Cancer, 2017, 17(1): 138. DOI:10.1186/s12885-017-3132-9
[5]
Cheng R, Lu C, Zhang G, et al. Overexpression of miR-203 increases the sensitivity of NSCLC A549/H460 cell lines to cisplatin by targeting Dickkopf-1[J]. Oncol Rep, 2017, 37(4): 2129-2136. DOI:10.3892/or.2017.5505
[6]
Li N, Ma Y, Ma L, et al. MicroRNA-488-3p sensitizes malignant melanoma cells to cisplatin by targeting PRKDC[J]. Cell Biol Int, 2017, 41(6): 622-629. DOI:10.1002/cbin.10765
[7]
Zhen Y, Fang W, Zhao M, et al. miR-374a-CCND1-pPI3K/AKT-c-JUN feedback loop modulated by PDCD4 suppresses cell growth, metastasis, and sensitizes nasopharyngeal carcinoma to cisplatin[J]. Oncogene, 2017, 36(2): 275-285. DOI:10.1038/onc.2016.201
[8]
Papangeli I, Kim J, Maier I, et al. MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation[J]. Nat Commun, 2016, 7: 11268. DOI:10.1038/ncomms11268
[9]
Dragoj M, Bankovic J, Sereti E, et al. Anti-invasive effects of CXCR4 and FAK inhibitors in non-small cell lung carcinomas with mutually inactivated p53 and PTEN tumor suppressors[J]. Invest New Drugs, 2017, 35(6): 718-732. DOI:10.1007/s10637-017-0494-4
[10]
Dai T, Hu Y, Zheng H. Hypoxia increases expression of CXC chemokine receptor 4 via activation of PI3K/Akt leading to enhanced migration of endothelial progenitor cells[J]. Eur Rev Med Pharmacol Sci, 2017, 21(8): 1820-1827
[11]
Hu J, Deng X, Bian X, et al. The expression of functional chemokine receptor CXCR4 is associated with the metastatic potential of human nasopharyngeal carcinoma[J]. Clin Cancer Res, 2005, 11(13): 4658-4665. DOI:10.1158/1078-0432.CCR-04-1798
Zheng H, Ma R, Wang Q, et al. MiR-625-3p promotes cell migration and invasion via inhibition of SCAI in colorectal carcinoma cells[J]. Oncotarget, 2015, 6(29): 27805-27815. DOI:10.18632/oncotarget.4738
[14]
Lu C, Shan Z, Hong J, et al. MicroRNA-92a promotes epithelial-mesenchymal transition through activation of PTEN/PI3K/AKT signaling pathway in non-small cell lung cancer metastasis[J]. Int J Oncol, 2017, 51(1): 235-244. DOI:10.3892/ijo.2017.3999
[15]
Liu J, Chen W, Chen Z, et al. The effects of microRNA-98 inhibits cell proliferation and invasion by targeting STAT3 in nasopharyngeal carcinoma[J]. Biomed Pharmacother, 2017, 93: 869-878. DOI:10.1016/j.biopha.2017.06.094
[16]
Zhang P, Hong H, Sun X, et al. MicroRNA-10b regulates epithelial-mesenchymal transition by modulating KLF4/Notch1/E-cadherin in cisplatin-resistant nasopharyngeal carcinoma cells[J]. Am J Cancer Res, 2016, 6(2): 141-156. DOI:10.1186/s12935-018-0508-0
[17]
Jiang C, Wang H, Zhou L, et al. MicroRNA-212 inhibits the metastasis of nasopharyngeal carcinoma by targeting SOX4[J]. Oncol Rep, 2017, 38(1): 82-88. DOI:10.3892/or.2017.5641
Miyoshi J, Toden S, Yoshida K, et al. MiR-139-5p as a novel serum biomarker for recurrence and metastasis in colorectal cancer[J]. Sci Rep, 2017, 7: 43393. DOI:10.1038/srep43393
[20]
Gu W, Li X, Wang J. miR-139 regulates the proliferation and invasion of hepatocellular carcinoma through the WNT/TCF-4 pathway[J]. Oncol Rep, 2014, 31(1): 397-404. DOI:10.3892/or.2013.2831
[21]
Testa JR, Bellacosa A. AKT plays a central role in tumorigenesis[J]. Proc Natl Acad Sci U S A, 2001, 98(20): 10983-10985. DOI:10.1073/pnas.211430998
[22]
Reeves PM, Abbaslou MA, Kools FRW, et al. CXCR4 blockade with AMD3100 enhances Taxol chemotherapy to limit ovarian cancer cell growth[J]. Anticancer Drugs, 2017, 28(9): 935-942. DOI:10.1097/CAD.0000000000000518
2018, Vol. 23 
