Yan Meidi, Zhang Lina, Li Guoqing, Xiao Shengwen, Dai Ji, Cen Xueying
Department of General Surgery, Ningbo No. 7 Hospital, Ningbo, Zhejiang, People's Republic of China.
Department of Preventive Medicine, Ningbo University, Ningbo, Zhejiang, People's Republic of China.
Biotechnol Appl Biochem. 2017 Jan;64(1):5-13. doi: 10.1002/bab.1461. Epub 2016 Apr 7.
Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer-related death in women globally. Its high morbidity and mortality, as well as its elevated tendency to metastasize to other organs, warrant the urgency to find new biomarkers for breast cancer diagnosis and treatment. The specific roles of long noncoding RNA linc-ITGB1 on cell proliferation and metastasis in breast cancer were explored in this study. The expression of linc-ITGB1 was significantly upregulated in both clinical breast cancer tissues and cultured breast cancer cell lines. The linc-ITGB1 knockdown with specific short hairpin RNA (shRNA) decreased cell proliferation and colony formation in vitro. Tumor growth in vivo was also inhibited by linc-ITGB1 depletion. In addition, linc-ITGB1 depletion caused cell accumulation in the G0/G1 phase. Breast cancer cell lines with linc-ITGB1 depletion exhibited decreased migration and invasion abilities compared with the control cells. Furthermore, the linc-ITGB1 knockdown decreased the expression of mesenchymal markers N-cadherin and vimentin while increasing the expression of the epithelial marker E-cadherin. Key cell cycle regulators Cdc25C and Cyclin B1 were also decreased by the linc-ITGB1 knockdown. These data suggest that linc-ITGB1 promotes breast cancer progression by inducing cell cycle arrest and interrupting the epithelial-to-mesenchymal transition process.
乳腺癌是全球女性中最常被诊断出的癌症，也是癌症相关死亡的主要原因。其高发病率和死亡率，以及向其他器官转移的倾向增加，使得寻找用于乳腺癌诊断和治疗的新生物标志物变得紧迫。本研究探讨了长链非编码RNA linc-ITGB1在乳腺癌细胞增殖和转移中的具体作用。linc-ITGB1在临床乳腺癌组织和培养的乳腺癌细胞系中的表达均显著上调。用特异性短发夹RNA（shRNA）敲低linc-ITGB1可降低体外细胞增殖和集落形成。体内肿瘤生长也因linc-ITGB1的缺失而受到抑制。此外，linc-ITGB1的缺失导致细胞在G0/G1期积累。与对照细胞相比，linc-ITGB1缺失的乳腺癌细胞系迁移和侵袭能力降低。此外，敲低linc-ITGB1可降低间充质标志物N-钙黏蛋白和波形蛋白的表达，同时增加上皮标志物E-钙黏蛋白的表达。关键细胞周期调节因子Cdc25C和细胞周期蛋白B1也因linc-ITGB1的敲低而减少。这些数据表明，linc-ITGB1通过诱导细胞周期停滞和中断上皮-间质转化过程来促进乳腺癌进展。
