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LncRNA FTX accelerates the progression of hepatocellular carcinoma by FTX/miR-374a-3p/HMGB1 pathway
Min Zhang1,2, Songman Yu1,2, Shang Gao1,2
1Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China.
Abstract:
The situation regarding Hepatocellular carcinoma (HCC) is severe, with high incidence and mortality rates worldwide. Abnormal expression of long noncoding RNAs (LncRNAs) has been implicated in the progression of malignant tumors. Although there are reports on LncRNA FTX (Lnc-FTX) in HCC, the findings are still contradictory, leaving its role unclear. This research aims to examine the relationship between Lnc-FTX expression and clinical prognosis in HCC, assess its impact on HCC cell biological functions, and elucidate the underlying mechanisms involved. Our findings demonstrate that patients in the high-expression group exhibit more severe TNM staging and poorer overall survival (OS) rates based on data from HCC patients in cohort 1 (n=27). Lnc-FTX expression is upregulated according to both the GSE 77314 and TCGA databases. This suggests that Lnc-FTX may serve as a potential prognostic biomarker for HCC. Overexpressed level of Lnc-FTX promotes proliferation, migration, and invasion while reducing the apoptotic rate in Hep3B and MHCC-LM3 cells. Conversely, the knockdown of Lnc-FTX yields opposite effects. RNA pulldown assay and mass spectrometry reveal that Lnc-FTX combines with RNA binding motif protein X-linked (RBMX), which in turn enhances the RNA stability of Lnc-FTX. Additionally, Lnc-FTX can sponge miR-374a-3p, thereby targeting High mobility group box 1 protein (HMGB1). In summary, high expression of Lnc-FTX possesses clinical value in predicting poor prognosis in HCC. As an oncogene, it promotes the malignant functions of HCC through the RBMX/Lnc-FTX interaction and the Lnc-FTX/miR-374a-3p/HMGB1 signaling pathway.
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