Wuxi School of Medicine, Jiangnan University, Wuxi, China.
School of Food Science and Technology, Jiangnan University, Wuxi, China.
Int J Biol Sci. 2020 Jan 1;16(1):162-171. doi: 10.7150/ijbs.36429. eCollection 2020.
Great quantity of intergenic noncoding RNAs (lncRNAs) have been identified in the mammalian genome and involved in various biological processes, especially in the development and metastasis of cancer. In this study, we identified one lncRNA, lncRNA NONHSAT028712 (Lnc712), was highly expressed in breast cancer cell lines and tissues based on microarray screening. Knockdown of Lnc712 largely inhibited breast cancer cell proliferation. Mechanistically, Lnc712 bound specifically to heat-shock protein 90 (HSP90). Interaction between Lnc712 and HSP90 is required for HSP90 binding to cell division cycle 37 (Cdc37). The Lnc712/HSP90/Cdc37 complex regulated cyclin-dependent kinase 2 (CDK2) activation and then triggered breast cancer cell proliferation. In summary, our results identified a new lncRNA regulate breast cancer proliferation though interaction with HSP90.
大量的基因间非编码 RNA（lncRNA）已在哺乳动物基因组中被鉴定出来，并参与了各种生物过程，特别是在癌症的发生和转移中。在这项研究中，我们通过微阵列筛选发现，一个 lncRNA，lncRNA NONHSAT028712（Lnc712）在乳腺癌细胞系和组织中高表达。Lnc712 的敲低极大地抑制了乳腺癌细胞的增殖。从机制上讲，Lnc712 特异性地与热休克蛋白 90（HSP90）结合。Lnc712 与 HSP90 之间的相互作用对于 HSP90 与细胞分裂周期蛋白 37（Cdc37）的结合是必需的。Lnc712/HSP90/Cdc37 复合物调节细胞周期蛋白依赖性激酶 2（CDK2）的激活，从而触发乳腺癌细胞的增殖。总之，我们的结果鉴定了一种新的 lncRNA，通过与 HSP90 的相互作用来调节乳腺癌的增殖。
