A novel biomarker NIFK-AS1 promotes hepatocellular carcinoma cell cycle progression through interaction with SRSF10

Huibin Song; Wenjing Li; Sixuan Guo; Zhentao He; Shi Liu; Yongsheng Duo

doi:10.21037/jgo-22-705

A novel biomarker NIFK-AS1 promotes hepatocellular carcinoma cell cycle progression through interaction with SRSF10

J Gastrointest Oncol. 2022 Aug;13(4):1927-1941. doi: 10.21037/jgo-22-705.

Authors

Huibin Song¹, Wenjing Li², Sixuan Guo³, Zhentao He⁴, Shi Liu⁴, Yongsheng Duo⁵

Affiliations

¹ Department of Emergency Surgery, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, China.
² Pharmacy School, Qiqihar Medical University, Qiqihar, China.
³ The Second Clinical College, Medical College of Nanchang University, Nanchang, China.
⁴ Department of General Surgery, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, China.
⁵ Department of Vascular Burn Surgery, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, China.

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most common carcinomas all over the world, with high mortality and low survival rate. Notably, many studies have showed that a variety of molecules play vital roles in the progression of HCC. Therefore, it is urgent to find reliable biomarkers to diagnose HCC and developing novel strategies are required for the effective treatment of patients with HCC.

Methods: This study obtained an HCC cohort from The Cancer Genome Atlas (TCGA). For prognostic analysis, the TCGA cohort was grouped according to different median boundaries. The key module associated with HCC was adopted by Weighted Gene Co-expression Network analysis (WGCNA). We also analyzed the survival ability, functional enrichment, and potential binding proteins of key lncRNAs. The expression of hub lncRNAs in HCC tissues and cell lines was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell Counting Kit-8 (CCK-8) and flow cytometry were applied to detect the cell proliferation, apoptosis, and cell cycle. The interaction between NIFK-AS1 and SRSF1 was examined using an RNA pull-down assay.

Results: The green module is the key module in HCC. NIFK-AS1 was highly expressed in HCC tissues and correlated with a poor prognosis in HCC patients (P=0.008). NIFK-AS1 was also significantly associated with cell mitosis, the cell cycle, and other biological processes. NIFK-AS1 deletion prevented cell proliferation, induced apoptosis, caused G2/M arrest, and affected cell cycle progression. RNA pull-down validated the NIFK-AS1/SRSF10 interaction. The overexpression of NIFK-AS1 was sufficient to rescue the growth of SRSF10 knockdown HepG2 cells.

Conclusions: This study suggested that NIFK-AS1 promotes HCC cell cycle progression through interaction with SRSF10 and its findings provide new insights into therapeutic targets for HCC.

Keywords: NIFK antisense RNA 1 (NIFK-AS1); SRSF10; hepatocellular carcinoma (HCC); long non-coding RNA (lncRNA).