Abstract
Human Hox genes (Homeobox) play a crucial role in embryonic development and cancer. The HOXC10 gene, a member of the HOX family, has been reported abnormally expressed in several cancers. However, the association between HOXC10 and hepatocellular carcinoma (HCC) remains to be elucidated. In the present study, tissue microarray cohort data showed that high levels of HOXC10 expression predicted a poor survival in HCC patients. Meanwhile, HOXC10 was significantly upregulated in the Huh7 cell line compared with the well differentiated cell line HepG2 and human normal liver cells. Functionally, silencing HOXC10 in Huh7 cells inhibited cell proliferation, increased apoptosis, and inhibited invasion and migration of HCC cells. HOXC10 overexpression in HepG2 cells increased cell proliferation, decreased apoptosis, and increased invasion and migration of HCC cells. In the HepG2 xenograft models, HOXC10 increased the tumor volume and weight compared with control. Mechanistically, the m6A modification of HOXC10 by METTL3 enhanced its expression by enhancing its mRNA stability. Both the in vitro and in vivo results showed that overexpressed HOXC10 activated the PTEN/AKT/mTOR pathway. In summary, the findings highlight the importance of HOXC10 in the regulation of HCC progression. HOXC10 is potentially a future therapeutic target for HCC treatment.
Highlights
HOXC10 is a potential prognostic biomarker for HCC patients.
HOXC10 upregulation in HCC could promote cell proliferation, migration and invasion.
HOXC10 function in HCC cells might be associated with the modulation of PTEN/AKT/mTOR signaling pathway.
M6A modification of HOXC10 by METTL3 enhanced its expression by enhancing its mRNA stability.
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Details
1 China Medical University, Department of Microbiology and Parasitology, College of Basic Medical Sciences, Shenyang, China (GRID:grid.412449.e) (ISNI:0000 0000 9678 1884)
2 The First Hospital of China Medical University, Key Laboratory of Diagnostic Imaging and Interventional Radiology of Liaoning Province, Department of Radiology, Shenyang, China (GRID:grid.412636.4)
3 China Medical University, Department of Medical Genetics, School of Life Sciences, Shenyang, China (GRID:grid.412449.e) (ISNI:0000 0000 9678 1884)




