Department of Cancer, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Neurosurgery, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin, China.
Cell Death Dis. 2023 Feb 3;14(2):80. doi: 10.1038/s41419-023-05628-z.
Increased glycolysis is one of the key metabolic hallmarks of cancer cells. However, the roles of lncRNAs in energy metabolism and cancer metastasis remain unclear. Here, the expression of TMEM105 associated with glycolysis was dramatically elevated from normal to breast cancer to breast cancer liver metastasis tissues, and the survival analysis revealed that high TMEM105 expression was related to poor survival, especially in patients with liver metastasis. Moreover, TMEM105 facilitated the glycolysis of breast cancer cells and induced cell invasion and breast cancer liver metastasis (BCLM). Mechanistically, TMEM105 regulated LDHA expression by sponging miR-1208, which further promoted cell glycolysis and BCLM. Importantly, glycolytic production of lactate enhanced TMEM105 expression in breast cancer cells by activating the SHH-MAZ signaling pathway. These findings suggested that the lactate-responsive TMEM105 acted as a miRNA sponge, inducing BCLM via a glycolysis-mediated positive feedback loop, which might be a rational target for the treatment of BCLM patients.
糖酵解增加是癌细胞的关键代谢特征之一。然而，lncRNAs 在能量代谢和癌症转移中的作用仍不清楚。在这里，与糖酵解相关的 TMEM105 的表达从正常组织到乳腺癌组织再到乳腺癌肝转移组织显著升高，生存分析显示高 TMEM105 表达与预后不良相关，特别是在发生肝转移的患者中。此外，TMEM105 通过海绵吸附 miR-1208 促进乳腺癌细胞的糖酵解，并诱导细胞侵袭和乳腺癌肝转移（BCLM）。在机制上，TMEM105 通过海绵吸附 miR-1208 调节 LDHA 的表达，从而进一步促进细胞糖酵解和 BCLM。重要的是，通过激活 SHH-MAZ 信号通路，乳酸酵解产物增强了乳腺癌细胞中 TMEM105 的表达。这些发现表明，乳酸反应性 TMEM105 作为一种 miRNA 海绵，通过糖酵解介导的正反馈环诱导 BCLM，这可能是治疗 BCLM 患者的合理靶点。
