LINC00184通过海绵化miR-1305提高CNTN1表达促进卵巢癌细胞增殖和顺铂耐药。
LINC00184 Promotes Ovarian Cancer Cells Proliferation and Cisplatin Resistance by Elevating CNTN1 Expression via Sponging miR-1305.
作者信息
Han Yuwen, You Jun, Han Yun, Liu Yinglei, Huang Menghui, Lu Xiaoyan, Chen Jingjing, Zheng Yanli
机构信息
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.
出版信息
Onco Targets Ther. 2021 Apr 19;14:2711-2726. doi: 10.2147/OTT.S280490. eCollection 2021.
OBJECTIVE
Cisplatin resistance is one of the main reasons for treatment failure in ovarian cancer (OC). Here, the effects of LINC00184 on cisplatin-resistant OC were studied.
PATIENTS AND METHODS
LINC00184, miR-1305 and CNTN1 expression in tissues from 70 OC patients was determined by qRT-PCR, in situ hybridization and Western blot. OC cell lines and OC cisplatin-resistant cell lines were cultured. Cells were transfected using Lipofectamine 2000 and treated with 100 nM cisplatin. Cell proliferation and apoptosis were researched by the CCK-8 assay and flow cytometry. A dual-luciferase reporter gene assay and RNA pull-down were performed to explore the relationship between two genes. LINC00184, miR-1305 and CNTN1 expression in cells was detected by qRT-PCR and Western blot. An in vivo experiment was conducted using nude mice. Ki67 and CNTN1 expression and apoptosis of xenograft tumors were investigated using immunohistochemistry and a TUNEL assay.
RESULTS
LINC00184 was up-regulated in OC clinical tissues and OC cells, especially in cisplatin-resistant OC patients and cells (<0.01 or <0.0001). LINC00184 overexpression significantly enhanced OC cell proliferation and cisplatin resistance, and inhibited OC cell apoptosis (<0.05 or <0.01). LINC00184 elevated CNTN1 expression via sponging miR-1305. LINC00184 overexpression markedly exacerbated the malignant phenotype of OC cells and cisplatin-resistant OC cells via the miR-1305/CNTN1 axis (<0.01). Silencing of LINC00184 significantly suppressed OC cell growth and cisplatin resistance in vivo (<0.01). LINC00184 silencing inhibited Ki67 and CNTN1 expression and promoted apoptosis of xenograft tumors. CNTN1 overexpression promoted proliferation and cisplatin resistance, and reduced apoptosis of OC cells (<0.05 or <0.01).
CONCLUSION
LINC00184 promoted OC cell proliferation and cisplatin resistance by elevating CNTN1 expression via sponging miR-1305.
目的
顺铂耐药是卵巢癌（OC）治疗失败的主要原因之一。在此，研究了LINC00184对顺铂耐药性OC的影响。
患者和方法
通过qRT-PCR、原位杂交和蛋白质印迹法测定70例OC患者组织中LINC00184、miR-1305和CNTN1的表达。培养OC细胞系和OC顺铂耐药细胞系。使用Lipofectamine 2000转染细胞并用100 nM顺铂处理。通过CCK-8测定法和流式细胞术研究细胞增殖和凋亡。进行双荧光素酶报告基因测定和RNA下拉实验以探索两个基因之间的关系。通过qRT-PCR和蛋白质印迹法检测细胞中LINC00184、miR-1305和CNTN1的表达。使用裸鼠进行体内实验。使用免疫组织化学和TUNEL测定法研究异种移植肿瘤的Ki67和CNTN1表达以及凋亡情况。
结果
LINC00184在OC临床组织和OC细胞中上调，尤其是在顺铂耐药的OC患者和细胞中（<0.01或<0.0001）。LINC00184过表达显著增强OC细胞增殖和顺铂耐药性，并抑制OC细胞凋亡（<0.05或<0.01）。LINC00184通过结合miR-1305提高CNTN1表达。LINC00184过表达通过miR-1305/CNTN1轴显著加剧OC细胞和顺铂耐药性OC细胞的恶性表型（<0.01）。沉默LINC00184在体内显著抑制OC细胞生长和顺铂耐药性（<0.01）。LINC00184沉默抑制异种移植肿瘤的Ki67和CNTN1表达并促进其凋亡。CNTN1过表达促进OC细胞增殖和顺铂耐药性，并减少其凋亡（<0.05或<0.01）。
结论
LINC00184通过结合miR-1305提高CNTN1表达，从而促进OC细胞增殖和顺铂耐药性。
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