Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Labor-atory of Surgical Translational Medicine, Changchun, China; Key Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, China.
Department of Hepatobiliary and Pancreatic Surgery, Second Hospital of Jilin University, Changchun, 130041, China.
Exp Cell Res. 2023 Apr 1;425(1):113514. doi: 10.1016/j.yexcr.2023.113514. Epub 2023 Feb 15.
Long non-coding RNAs (lncRNAs) play an important role in regulating several physiological processes and have been implicated in several pathologies including cancer. LncRNAs have been found to regulate key cellular pathways involved in cancer development, and their aberrant expression plays critical roles in the onset or progression of disease. The role of lncRNAs in breast cancer (BC) has become a hot topic of research in recent years. We previously showed that LINC00365 inhibits BC survival. In the current study, based on the important role of energy metabolism and HIF-1α for tumor cell proliferation, we investigated the role and mechanism of the LINC00365/HIF-1α axis in affecting tumor growth through glycolysis using the breast cancer cell lines MCF-7 and HCC-1937. We found that LINC00365 inhibited BC cell proliferation. Furthermore, LINC00365 overexpression suppressed aerobic glycolysis in BC cells. RNA-sequencing identified hypoxia-inducible factor-1α (HIF-1α), which has been linked with glycolysis and upregulates glycolysis-related genes, as a potential target gene of LINC00365. Accordingly, we found that LINC00365 overexpression resulted in decreased expression of key glycolytic enzymes such as downstream hexokinase 2 (HK2), recombinant pyruvate kinase isozymes M2 (PKM2) and lactate dehydrogenase A (LDHA). Our results suggest that targeting LINC00365 may reverse the glucose metabolism pattern of BC and effectively inhibit BC survival both in vitro and in vivo.
长链非编码 RNA（lncRNA）在调节多种生理过程中发挥着重要作用，并与包括癌症在内的多种病理学有关。已经发现 lncRNA 调节参与癌症发展的关键细胞途径，其异常表达在疾病的发生或进展中起着关键作用。lncRNA 在乳腺癌（BC）中的作用近年来成为研究热点。我们之前表明，LINC00365 抑制 BC 细胞的存活。在当前的研究中，基于能量代谢和 HIF-1α 对肿瘤细胞增殖的重要作用，我们通过使用乳腺癌细胞系 MCF-7 和 HCC-1937 研究了 LINC00365/HIF-1α 轴通过糖酵解影响肿瘤生长的作用和机制。我们发现 LINC00365 抑制 BC 细胞的增殖。此外，LINC00365 的过表达抑制了 BC 细胞的有氧糖酵解。RNA 测序鉴定出与糖酵解相关并上调糖酵解相关基因的缺氧诱导因子-1α（HIF-1α），是 LINC00365 的潜在靶基因。因此，我们发现 LINC00365 的过表达导致下游己糖激酶 2（HK2）、重组丙酮酸激酶同工酶 M2（PKM2）和乳酸脱氢酶 A（LDHA）等关键糖酵解酶的表达降低。我们的结果表明，靶向 LINC00365 可能会改变 BC 的葡萄糖代谢模式，并有效抑制 BC 的体外和体内存活。
