Long noncoding RNA MIR210HG is induced by hypoxia-inducible factor 1α and promotes cervical cancer progression

作者：Hu, Xiao-Lin; Huang, Xia-Tong; Zhang, Jia-Ni; Liu, Jie; Wen, Li-Jun; Xu, Xin; Zhou, Jue-Yu^*

来源：American Journal of Cancer Research, 2022, 12(6): 2783-+.

• Cervical squamous cell carcinoma
• long noncoding RNA
• MIR210HG
• hypoxia
• HIF-1 alpha

Increasing evidence has indicated that long noncoding RNAs (lncRNAs) play essential roles in various types of cancer, especially the ability of tumor cells to adapt to hypoxia conditions. However, only a few of them have been experimentally validated in cervical squamous cell carcinoma (CSCC). In the current study, we identified a hypoxia-induced lncRNA MIR210HG was excessively expressed in CSCC tissues and regulated by human papillomavirus (HPV) type 16 E6 and E7 via hypoxia-inducible factor 1 alpha (HIF-1 alpha). Functional assays revealed the role of MIR210HG in promoting proliferation, migration and invasion of CSCC cells in vitro under normoxia as well as hypoxia conditions. Meanwhile, stable MIR210HG silencing dramatically repressed tumor growth and pulmonary metastasis in vivo. Mechanistically, the depletion of MIR210HG or HIF-1 alpha decreased each other's expression level, while silencing MIR210HG or HIF-1 alpha respectively downregulated the expression levels of phosphoglycerate kinase 1 (PGK1), one of key metabolic enzymes in the glycolysis pathway. Furthermore, decreased expression of PGK1 by HIF-1 alpha knockdown was reversed through the overexpression of MIR210HG. Also, we demonstrated HIF-1 alpha can activate the transcription of MIR210HG via binding its promoter. Taken together, these results expand our understanding of the cancer-associated functions of hypoxia-induced lncRNAs, and highlight MIR210HG forms a feedback loop with HIF-1 alpha contributing to cervical carcinogenesis, with potential implications for therapeutic targeting.

• 单位
  1; 南方医科大学