长链非编码RNA TCONS_l2_00002973与较低的肿瘤分期和良好的生存率相关，并且在三阴性乳腺癌中还能抑制癌细胞增殖，同时增强细胞凋亡。

LncRNA TCONS_l2_00002973 correlates with less advanced tumor stage and favorable survival, and also inhibits cancer cells proliferation while enhancing apoptosis in triple-negative breast cancer.

作者信息

Yan Jiaqi, Wang Rui, Wu Zhiyong

机构信息

Department of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

J BUON. 2019 Mar-Apr;24(2):535-542.

PMID:31128002

Abstract

PURPOSE

This study aimed to investigate the correlation of long non-coding RNA (lncRNA) TCONS_l2_00002973 expression with clinicopathological features as well as overall survival (OS) in triple-negative breast cancer (TNBC) patients, and further explore the regulatory effect of lncRNA TCONS_l2_00002973 on cells' proliferation and apoptosis in TNBC cells.

METHODS

96 TNBC patients undergoing surgery were consecutively enrolled in this prospective cohort study. LncRNA TCONS_l2_00002973 expression in tumor tissue sample and adjacent non-tumor sample was detected by qPCR. Normal control (NC) shRNA (NC(-) group), lncRNA TCONS_l2_00002973 shRNA (Lnc(-) group), NC overexpression (NC(+) group) and lncRNA TCONS_l2_00002973 overexpression plasmids (Lnc(+) group) were transfected into MDA-MB-231 breast cancer cells. Cell proliferation ability, cell apoptosis rate and apoptosis-related protein expressions were detected using CCK-8 assay, annexin V (AV)/propidium iodide (PI) assay and Western blot assay respectively.

RESULTS

LncRNA TCONS_l2_00002973 expression was lower in tumor tissue compared to paired adjacent tissue (p<0.001), and its low expression was associated with increased T stage (p=0.002), raised N stage (p=0.003) and advanced TNM stage (p=0.005) in TNBC patients. Poor OS was found in lncRNA TCONS_l2_00002973 low expression group compared to lncRNA TCONS_l2_00002973 high expression group (p=0.006). Further in vitro experiments disclosed that lncRNA TCONS_l2_00002973 expression was reduced in various breast cancer cell lines compared to normal breast cell line, and lncRNA TCONS_l2_00002973 repressed cell proliferation and enhanced cells apoptosis in MDA-MB-231 cells.

CONCLUSIONS

LncRNA TCONS_l2_00002973 correlates with less advanced tumor stage and favorable survival, and it also inhibits cancer cells proliferation while enhances apoptosis in TNBC.

摘要

目的

本研究旨在探讨长链非编码RNA（lncRNA）TCONS_l2_00002973表达与三阴性乳腺癌（TNBC）患者临床病理特征及总生存期（OS）的相关性，并进一步探究lncRNA TCONS_l2_00002973对TNBC细胞增殖和凋亡的调控作用。

方法

96例行手术的TNBC患者连续纳入本前瞻性队列研究。采用qPCR检测肿瘤组织样本和相邻非肿瘤样本中lncRNA TCONS_l2_00002973的表达。将正常对照（NC）短发夹RNA（NC(-)组）、lncRNA TCONS_l2_00002973短发夹RNA（Lnc(-)组）、NC过表达载体（NC(+)组）和lncRNA TCONS_l2_00002973过表达质粒（Lnc(+)组）分别转染至MDA-MB-231乳腺癌细胞。分别采用CCK-8法、膜联蛋白V（AV）/碘化丙啶（PI）法和蛋白质免疫印迹法检测细胞增殖能力、细胞凋亡率及凋亡相关蛋白表达。

结果

与配对的相邻组织相比，肿瘤组织中lncRNA TCONS_l2_00002973表达较低（p<0.001），其低表达与TNBC患者T分期增加（p=0.002）、N分期升高（p=0.003）及TNM分期进展（p=0.005）相关。lncRNA TCONS_l2_00002973低表达组的OS较lncRNA TCONS_l2_00002973高表达组差（p=0.006）。进一步的体外实验表明，与正常乳腺细胞系相比，多种乳腺癌细胞系中lncRNA TCONS_l2_00002973表达降低，且lncRNA TCONS_l2_00002973抑制MDA-MB-231细胞增殖并增强细胞凋亡。