Long non coding RNA00844 inhibits MAPK signaling to suppress the progression of hepatocellular carcinoma by targeting AZGP1.
Background Previous data have confirmed that disordered long non coding ribonucleic acid (lncRNA) expression is evident in many cancers and is correlated with tumor progression. The present study aimed to investigate the function of long non coding RNA00844 (LINC00844) in hepatocellular carcinoma (HCC) Methods The expression levels of target genes were detected with real time polymerase chain reaction (PCR) and western blotting. The biologic function of HCC cells was determined with cell viability assay, colony formation assay, cell cycle analysis, apoptosis detection, and Transwell migration assay in vitro. Tumorigenesis was performed with cell injection in vivo. The relationship between LINC00844 and survival outcomes was determined with the Cox proportional hazards model. A RNA precipitation assay was conducted to reveal the types of LINC00844 that potentially bind with proteins. Results LINC00844 was found to be significantly decreased in HCC tissue and was correlated with poor tumor characteristics, such as portal vein invasion, high a fetoprotein (AFP) and a high rate of tumor recurrence. Exotic LINC00844 expression in HCC cell lines significantly suppressed proliferation and migration, as well as invasiveness, whereas LINC00844 deletion had the opposite effect. LINC00844 overexpression significantly inhibited HCC tumorigenesis in vivo. Mechanistic analyses indicated that the mitogen activated protein kinase (MAPK) signaling pathway was remarkably inactivated by LINC00844. Furthermore, the immunoprecipitation assay verified that LINC00844 can bind to zinc alpha 2 glycoprotein (AZGP1) and interfere with its translocation. LINC00844 can also promote AZGP1 expression, leading to the suppression of the transforming growth factor b1 (TGF b1) extracellular signal regulated kinase (ERK) pathway. Conclusions LINC00844 is a novel anti oncogene in the development of HCC and a potentially promising therapeutic target in HCC.
Annals of translational medicine