LncRNA RP11-620J15.3 promotes HCC cell proliferation and metastasis by targeting miR-326/GPI to enhance glycolysis

Abstract

Background Accumulating studies have demonstrated that the Warburg effect plays a central role in the occurrence and development of hepatocellular carcinoma (HCC), albeit the role of non-coding RNA (lncRNA) in its association remains unclear. Methods The Zhengzhou University People’s Hospital kindly provided 80 pairs of HCC tissues and their matched paracancerous tissues for this study. Bioinformatics analysis, real-time quantitative polymerase chain reaction, Western blotting, and oncology functional assays were performed to determine the contribution of RP11-620J15.3 to the development of HCC. The mechanism of co-immunoprecipitation and a luciferase reporter gene was employed to ascertain how RP11-620J15.3 interacts with important molecular targets. Results Our results revealed that a lncRNA termed RP11-620J15.3 was overexpressed in HCC and was substantially associated with the tumor size. A high expression of RP11-620J15.3 mRNA was found to be significantly associated with worsening prognosis in HCC patients. We discovered that RP11-620J15.3 stimulated the glycolytic pathway in HCC cells by RNA-sequencing (RNA-seq) and metabolomics analyses. Mechanistically, RP11-620J15.3 acted as a competitive endogenous RNA to regulate the GPI expression by sponging miR-326 in HCC. In addition, TBP acted as a transcription factor for RP11-620J15.3, which contributed to the high expression of RP11-620J15.3 in HCC cells. Conclusion Based on our findings, lncRNA RP11-620J15.3 is a novel LncRNA that positively regulates tumor progression. Specifically, RP11-620J15.3/miR-326/GPI pathway promotes HCC malignant progression by regulating glycolysis, thereby providing novel targets for HCC treatment and drug development.

Comprehensive analysis of differentially expressed miRNAs in Hepatocellular carcinoma: prognostic significance and pathway insights

“…In parallel with the results on putative oncogenic miRNAs, our results on putative tumour suppressors agree with pre-clinical results. Mir-3653 , mir-326 and mir-139 have been shown to inhibit metastasis and progression of HCC cells (27), (28), (29). Similarly, mir-145 has been implicated in G2/M phase arrest by inhibiting cyclin B1 (30).…”

Comprehensive analysis of differentially expressed miRNAs in hepatocellular carcinoma: Prognostic, predictive significance and pathway insights

“…In parallel with the results on putative oncogenic miRNAs, our results on putative tumour suppressors agree with pre-clinical results. Mir-3653, mir-326 and mir-139 have been shown to inhibit metastasis and progression of HCC cells [29][30][31]. Similarly, mir-145 has been implicated in G2/M phase arrest by inhibiting cyclin B1 [32].…”

Disulfidptosis-related lncRNA signature reveals immune microenvironment and novel molecular subtyping of stomach adenocarcinoma

“…Significant progress has been made in recent years in optimizing delivery strategies and chemical modification technologies for targeting lncRNAs, including the utilization of polymers, lipid nanoparticles, and extracellular vesicles (EXs) [ 11 , 12 ]. These approaches for lncRNA targeting have proven to be more accessible and efficient compared to the development of specific protein binding inhibitors [ 11 , 12 ]. Therefore, the discovery of lncRNA biomarkers in gastric cancer holds even greater potential, as it can easily translate into effective targets for clinical application.…”