CircSMYD4 regulates proliferation, migration and apoptosis of hepatocellular carcinoma cells by sponging miR-584-5p
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Cancer Cell International Open Access
PRIMARY RESEARCH
CircSMYD4 regulates proliferation, migration and apoptosis of hepatocellular carcinoma cells by sponging miR‑584‑5p Yanhe Zhang1, Hui Wang1, Chao Li1, Linlin Gao1, Yayun Zheng1, Wenjuan Chang1, Chao Lu1 and Xiaoguang Zhao2*
Abstract Background: There is evidence that circSMYD4 is differentially expressed in hepatocellular carcinoma (HCC), but its mechanism of action remains unclear. Therefore, this study aimed to explore the role of circSMYD4 in the occurrence and development of HCC and its specific molecular mechanism. Methods: The expressions of related genes and proteins in the development of HCC were detected by real-time quantitative-PCR and Western blot. HCC cells treated with RNase R and Actinomycin D were used to examine the stability of circSMYD4. Bioinformatics analysis, RNA pull-down assay, luciferase assay and Spearman correlation analysis were performed to evaluate the interaction between circSMYD4 and miRNA. Cell Counting Kit-8, clone formation assay, wound healing assay, Transwell, flow cytometry, nude tumor formation experiment, and immunohistochemistry were employed to analyze the function of circSMYD4 in HCC. A rescue experiment was conducted to analyze the effect of miR-584-5p on the physiological functions of cells. Results: CircSMYD4 was down-regulated in HCC tissues and cells, and was not easily affected by RNase R and Actinomycin D. The abundances of circSMYD4 and SMYD4 in the cytoplasm were significantly higher than in the nucleus. Up-regulation of circSMYD4 inhibited the proliferation, invasion and migration and promoted the apoptosis of HCC cells in vitro, while it inhibited tumor growth, promoted apoptosis-related proteins, and suppressed alpha-fetoprotein (AFP) levels in vivo. CircSMYD4 could be used as a miRNA sponge to target miR-584-5p. In addition, miR-584-5p overexpression partially reversed the regulatory effect of circSMYD4 on HCC. Conclusion: CircSMYD4 prevents the development of HCC through regulating multiple signaling pathways such as metastasis and apoptosis by sponging miR-584-5p. Keywords: Hepatocellular carcinoma, CircSMYD4, miR-584-5p, Circular RNA, Proliferation Introduction Liver cancers are the fourth most common cause of cancer-related deaths worldwide, and it ranks sixth in incidence cases. According to annual forecasts, the World Health Organization estimates that more than *Correspondence: [email protected] 2 Department of Medical Oncology, Jiaozuo People’s Hospital, No. 267, Middle Jiefang Road, Shanyang District, Jiaozuo 454002, China Full list of author information is available at the end of the article
1 million patients will die of liver cancer in 2030 [1]. Hepatocellular carcinoma (HCC), which typically develops on a background of chronic liver disease, is the most important type of primary liver cancer [2]. The development of HCC is a complex multistep process involving persistent inflammatory damage, including hepatocyte necrosis and regeneration associated with fibrotic deposition [2]. I
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