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LncRNA SNHG6 promotes G1/S-phase transition in hepatocellular carcinoma by impairing miR-204-5p-mediated inhibition of E2F1

Abstract

Emerging evidence suggests that long noncoding RNAs (lncRNAs) function as competitive endogenous RNA (ceRNA) targeting proteins and genes; however, the role of lncRNAs in hepatocellular carcinoma (HCC) is not well understood. We investigated the mechanism by which lncRNA SNHG6 promotes the development of HCC. RT-qPCR revealed upregulated lncRNA SNHG6 in the HCC setting. Elevated SNHG6 expression was indicative of poor prognosis in patients with HCC. SNHG6 overexpression resulted in increased cyclin D1, cyclin E1, and E2F1 expression both in vitro and in vivo. SNHG6 also promoted HCC cell proliferation by enhancing G1-S phase transition in vitro. Dual luciferase reporter assays, RIP, and RNA pull-down assays demonstrated SNHG6 competitively bound to miR-204-5p and inhibited its expression preventing miR-204-5p from targeting E2F1. Overexpression of miR-204-5p abolished the effect of SNHG6. Our data suggest that SNHG6 functions as a ceRNA that targets miR-204-5p resulting in an increased E2F1 expression and enhanced G1-S phase transition, thereby promoting the tumorigenesis of HCC.

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Fig. 1: SNHG6 promotes HCC cell proliferation.
Fig. 2: Downregulation of SNHG6 suppresses the proliferation of HCC cell lines.
Fig. 3: SNHG6 promotes cell cycle progression.
Fig. 4: SNHG6 promotes tumor growth in vivo.
Fig. 5: SNHG6 acts as a sponge of miR-204-5p and downregulates its expression in vitro.
Fig. 6: SNHG6 inhibits the expression of miR-204-5p whereby elevating E2F1 expression.
Fig. 7: SNHG6 promotes HCC progression by upregulating E2F1.
Fig. 8: Schematic diagram of the SNHG6-miR-204-5p-E2F1 regulatory network and its implications in the progression of HCC.

Data availability

The datasets generated/analyzed during the current study are available.

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Acknowledgements

The authors would like to acknowledge the helpful comments on this paper received from the reviewers.

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YH and KC designed the study. JG and RL collated the data, carried out data analyses, and produced the initial draft of the manuscript. YL and HY contributed to drafting the manuscript. All authors have read and approved the final submitted manuscript.

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Correspondence to Hongji Yang or Jun Gong.

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The authors declare no competing interests.

Ethics approval and consent to participate

Study protocols were approved by the Ethics Committee of Sichuan Provincial People’s Hospital and conducted in compliance with the ethical principles for medical research involving human subjects described in the Declaration of Helsinki. Written, informed consent was obtained from all patients or their relatives prior to entering the study and all patient-specific data are kept confidential. Animal experiments were approved by the Animal Ethics Committee of Sichuan Provincial People’s Hospital and performed according to the Guide for the Ethical Care and Use of Laboratory Animals published by the US National Institutes of Health. Extensive efforts were made to ensure animals were subjected to the minimum amount of suffering possible.

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Chen, K., Hou, Y., Liao, R. et al. LncRNA SNHG6 promotes G1/S-phase transition in hepatocellular carcinoma by impairing miR-204-5p-mediated inhibition of E2F1. Oncogene 40, 3217–3230 (2021). https://doi.org/10.1038/s41388-021-01671-2

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