Li L, Xu Q-H, Dong Y-H, Li G-X, Yang L, Wang L-W, Li H-Y
Department of Obstetrics and Gynecology, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Eur Rev Med Pharmacol Sci. 2016 May;20(10):2004-10.
Elevated miR-181a is associated with the transition of ovarian tissues from normal into a cancerous state. However, its regulative effect on multidrug resistance (MDR) of ovarian cancer is not quite clear. Therefore, this study aimed to investigate its regulative effects on epithelial-to-mesenchymal transition (EMT) and MDR in ovarian cancer.
The expression profile of miR-181a in normal and ovarian cancer tissues was firstly quantified using qRT-PCR analysis. Then, human ovarian cancer cell line SKOV3 were transfected for miR-181a overexpression and the paclitaxel-resistant variant SKOV3/PTX cells were transfected for miR-181a knockdown. The effect of miR-181a overexpression/knockdown on EMT and PTX sensitivity were studied.
MiR-181a level in chemoresistant (CR) cancer tissues were significantly higher than in chemosensitive (CS) cancer tissues and in normal tissue. SKOV3/PTX cells had significantly higher expression of miR-181a and N-cadherin than SKOV3 cells. SKOV3 cells had decreased E-cadherin expression and increased N-cadherin expression after enforced miR-181a expression, while SKOV3/PTX cells had increased E-cadherin expression and decreased N-cadherin expression after miR-181a knockdown. SKOV3 cells had increased P-gp expression after enforced miR-181a expression. Following MTT assay and flow cytometry analysis both confirmed that miR-181a overexpression decreased the PTX sensitivity of SKOV3 cells and while miR-181a inhibition increased the sensitivity of SKOV3/PTX cells.
MiR-181a is an important oncomiR significantly increased in chemoresistant ovarian cancer. Its upregulation is associated with increased level of EMT and decreased cell apoptosis induced by PTX treatment.
miR-181a水平升高与卵巢组织从正常状态转变为癌状态相关。然而，其对卵巢癌多药耐药性（MDR）的调节作用尚不完全清楚。因此，本研究旨在探讨其对卵巢癌上皮-间质转化（EMT）和MDR的调节作用。
首先采用qRT-PCR分析定量正常和卵巢癌组织中miR-181a的表达谱。然后，对人卵巢癌细胞系SKOV3进行miR-181a过表达转染，对紫杉醇耐药变体SKOV3/PTX细胞进行miR-181a敲低转染。研究miR-181a过表达/敲低对EMT和紫杉醇敏感性的影响。
化疗耐药（CR）癌组织中的miR-181a水平显著高于化疗敏感（CS）癌组织和正常组织。SKOV3/PTX细胞中miR-181a和N-钙黏蛋白的表达明显高于SKOV3细胞。强制表达miR-181a后，SKOV3细胞中E-钙黏蛋白表达降低，N-钙黏蛋白表达增加，而敲低miR-181a后，SKOV3/PTX细胞中E-钙黏蛋白表达增加，N-钙黏蛋白表达降低。强制表达miR-181a后，SKOV3细胞中P-糖蛋白表达增加。MTT法和流式细胞术分析均证实，miR-181a过表达降低了SKOV3细胞对紫杉醇的敏感性，而抑制miR-181a则增加了SKOV3/PTX细胞的敏感性。
miR-181a是一种重要的癌基因，在化疗耐药的卵巢癌中显著增加。其上调与EMT水平升高和紫杉醇治疗诱导的细胞凋亡减少有关。
