LncRNA CYTOR promotes cell proliferation and tumor growth via miR-125b/SEMA4C axis in hepatocellular carcinoma.

Qing Tian,Yamin Zhang,Xiaodong Yan,Zheyue Yuan,Zirong Liu,Long Yang

doi:10.3892/ol.2021.13057

Qing Tian, Yamin Zhang + Show 4 more

Open Access

https://doi.org/10.3892/ol.2021.13057

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Abstract

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide with high morbidity and high mortality rates. Previous studies have demonstrated that cytoskeleton regulator RNA (CYTOR) plays critical roles in the tumorigenesis of various types of cancer. The present study aimed to investigate the clinical significance, biological function and molecular mechanism of CYTOR in the progression of HCC. The expression level of CYTOR was determined by reverse transcription quantitative PCR in HCC tissues and cell lines. The biological function of CYTOR was investigated using CCK-8 assay, EdU immunofluorescence, western blotting and TUNEL assay in vitro. A xenograft tumor model and immunohistochemistry were used to validate the role of CYTOR in vivo. The downstream targets of CYTOR and micro-RNA (miR)-125b were confirmed by RNA immunoprecipitation assay and luciferase reporter assays. The results demonstrated that CYTOR was significantly increased in HCC tissues compared with non-tumor tissues and that CYTOR expression was associated with the poor prognosis of patients with HCC. Furthermore, CYTOR silencing could inhibit the proliferation and promote the apoptosis of HCC cells. CYTOR overexpression had the opposite effects. The results from in vivo xenograft demonstrated that CYTOR knockdown suppressed tumor growth. In addition, CYTOR could directly interact with and negatively regulate miR-125b. Furthermore, semaphorin 4C (SEMA4C) was the target of miR-125b and CYTOR regulated SEMA4C expression by modulating miR-125b. Taken together, the findings from the present study demonstrated that CYTOR could promote cell proliferation and tumor growth by sponging miR-125b and upregulating SEMA4C, which suggested that CYTOR may act as a potential therapeutic target in HCC.

Highlights

Hepatocellular carcinoma (HCC) is one of the most common hepatic malignancies and remains the leading cause of cancer‐associated mortality worldwide [1,2]
The results demonstrated that cytoskeleton regulator RNA (CYTOR) expression was significantly increased in HCC tumor tissues compared with adjacent non‐tumor tissues (Fig. 1A)
These findings indicated that CYTOR upregulation was closely asso ciated with the poor prognosis of patients with HCC and that it may be involved in HCC progression

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common hepatic malignancies and remains the leading cause of cancer‐associated mortality worldwide [1,2]. The expression of the lncRNA SOX9 antisense RNA 1 (SOX9‐AS1) is increased in HCC and might have a prognostic significance in patients with HCC. A previous study identified the functional lncRNA cytoskeleton regulator RNA (CYTOR), known as Linc00152, which is situated on human chromo some 2p11.2 and which abnormal expression is related to the inflammatory response and apoptosis [10]. Previous studies have reported that CYTOR plays a pivotal role in the devel opment of various cancers, including colorectal cancer [11], breast cancer [12] and lung cancer [13], in which it functions as an oncogenic lncRNA. The biological role and underlying mechanism of CYTOR in HCC cell proliferation and apoptosis remain unknown

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