LYRM2 Promotes the Growth and Metastasis of Hepatocellular Carcinoma via Enhancing HIF-1α-Dependent Glucose Metabolic Reprogramming.

Hepatocellular carcinoma (HCC) is a foetal malignancy with dismal overall survival. The molecular mechanism underlying the progression of HCC remain largely unknown. LYR motif containing 2 (LYRM2) has been identified as an oncogene in colorectal cancer; however, its expression, functions and molecular mechanism in the context of HCC has not been investigated. Data derived from The Cancer Gemome Atlas, along with findings from our patients' cohort, indicate that LYRM2 expression is elevated in HCC tissues and correlates with adverse clinicopathological features and prognosis in HCC patients. Subsequent research into the biological functions of LYRM2 has revealed that it promotes the proliferation, migration, invasion and epithelial-mesenchymal transition of HCC cells, both in vitro and in vivo. Mechanistic insights have shown that LYRM2 interacts with HIF-1α, enhancing the protein stability of HIF-1α, which in turn increases cellular glycolysis and inhibits mitochondrial respiration. Moreover, the glucose metabolic reprogramming mediated by LYRM2 is implicated in its role in promoting HCC growth and metastasis. Collectively, this study identifies that LYRM2 as a novel oncogenic protein in HCC and elucidates its contribution to HCC progression through enhancing HIF-1α-dependent glucose metabolic reprogramming.