Department of Medical Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
Department of Medical Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Oncology Hospital, Xi'an International Medical Center Hospital, Xi'an, Shaanxi 710075, China.
Pathol Res Pract. 2020 Sep;216(9):153103. doi: 10.1016/j.prp.2020.153103. Epub 2020 Jul 10.
Laryngeal squamous cell carcinoma (LSCC) accounts for about 85%-90% of all cases of laryngeal cancer. So far, the role and molecular mechanism of circular RNA 0,000,218 (circ_0000218)/microRNA (miR)-139-3p in laryngeal cancer are not clear. The present study aimed to investigate the role and regulatory mechanism of circ_0000218/miR-139-3p in laryngeal cancerin vitro and in vivo.
quantitative real time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ_0000218/miR-139-3p in LSCC cells. Dual luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to confirm binding sites between miR-139-3p and smad family member 3 (Smad3), and circ_0000218 and miR-139-3p. Cell Counting Kit-8 (CCK-8) and cell apoptosis analysis were used to detect cell viability and apoptosis. Xenograft experiment was performed to show in vivo effect of circ_0000218/miR-139-3p on the growth of LSCC.
Circ_0000218 was highly expressed in LSCC cells. miR-139-3p, lower expressed in LSCC cells, was negatively regulated by circ_0000218 in LSCC cells. Besides, the findings suggested that circ_0000218 silencing inhibited the LSCC cell viability and promoted apoptosis by negatively regulating miR-139-3p expression. Furthermore, the data indicated that miR-139-3p inhibited the viability of LSCC cells and promoted apoptosis, and these effects were reversed by Smad3 over-expression. In addition, the in vivo effects of circ_0000218/miR-139-3p on LSCC were consistent with the in vitro study.
circ_0000218 inhibition inhibited the growth of LSCC by targeting miR-139-3p/Smad3 axis. Our present study provided a new target for laryngeal cancer treatment.
喉鳞状细胞癌(LSCC)约占所有喉癌病例的 85%-90%。到目前为止,环状 RNA 0,000,218(circ_0000218)/微小 RNA(miR)-139-3p 在喉癌中的作用和分子机制尚不清楚。本研究旨在探讨 circ_0000218/miR-139-3p 在喉癌细胞中的体外和体内作用及其调控机制。
采用实时定量聚合酶链反应(qRT-PCR)检测 LSCC 细胞中 circ_0000218/miR-139-3p 的表达。双荧光素酶报告基因检测和 RNA 免疫沉淀(RIP)实验验证 miR-139-3p 与 Smad 家族成员 3(Smad3)和 circ_0000218 与 miR-139-3p 的结合位点。细胞计数试剂盒-8(CCK-8)和细胞凋亡分析检测细胞活力和凋亡。进行异种移植实验以显示 circ_0000218/miR-139-3p 对 LSCC 生长的体内作用。
circ_0000218 在 LSCC 细胞中高表达。miR-139-3p 在 LSCC 细胞中低表达,可被 circ_0000218 在 LSCC 细胞中负调控。此外,研究表明,circ_0000218 沉默通过负调控 miR-139-3p 的表达抑制 LSCC 细胞的活力并促进凋亡。进一步表明,miR-139-3p 抑制 LSCC 细胞的活力并促进凋亡,而 Smad3 的过表达可逆转这些作用。此外,circ_0000218/miR-139-3p 对 LSCC 的体内作用与体外研究一致。
circ_0000218 通过靶向 miR-139-3p/Smad3 轴抑制 LSCC 的生长。本研究为喉癌的治疗提供了新的靶点。