Yan Jiaqi, Wang Rui, Wu Zhiyong
Department of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J BUON. 2019 Mar-Apr;24(2):535-542.
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.
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.
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.
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.
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。
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。
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。
lncRNA TCONS_l2_00002973与肿瘤分期较晚及预后良好相关，且在TNBC中抑制癌细胞增殖并增强凋亡。
