OncoTargets and Therapy (Apr 2021)
LINC00184 Promotes Ovarian Cancer Cells Proliferation and Cisplatin Resistance by Elevating CNTN1 Expression via Sponging miR-1305
Abstract
Yuwen Han, Jun You, Yun Han, Yinglei Liu, Menghui Huang, Xiaoyan Lu, Jingjing Chen, Yanli Zheng Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, People’s Republic of ChinaCorrespondence: Yanli ZhengDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Nantong University, No. 6 North Hai-Er-Xiang Road, Chongchuan District, Nantong, 226001, Jiangsu Province, People’s Republic of ChinaTel +86-0513-85061000Email [email protected]: 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 (p< 0.01 or p< 0.0001). LINC00184 overexpression significantly enhanced OC cell proliferation and cisplatin resistance, and inhibited OC cell apoptosis (p< 0.05 or p< 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 (p< 0.01). Silencing of LINC00184 significantly suppressed OC cell growth and cisplatin resistance in vivo (p< 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 (p< 0.05 or p< 0.01).Conclusion: LINC00184 promoted OC cell proliferation and cisplatin resistance by elevating CNTN1 expression via sponging miR-1305.Keywords: OC, cisplatin resistance, LINC00184, miR-1305, CNTN1
