Overexpression of circ_0001445 decelerates hepatocellular carcinoma progression by regulating miR-942-5p/ALX4 axis

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ORIGINAL RESEARCH PAPER

Overexpression of circ_0001445 decelerates hepatocellular carcinoma progression by regulating miR-942-5p/ALX4 axis Qinhong Xu . Lijing Zhou . Ganghua Yang . Fandi Meng . Yong Wan . Lin Wang . Lei Zhang

Received: 2 April 2020 / Accepted: 8 August 2020 Ó Springer Nature B.V. 2020

Abstract Circular RNAs (circRNAs) have been verified to have essential regulatory roles in diverse human cancers, including hepatocellular carcinoma (HCC). In this study, we aimed to explore the roles of circ_0001445 in HCC. Herein, circ_0001445 was decreased and miR-942-5p was increased in HCC tissues and cells. Circ_0001445 overexpression or miR-942-5p inhibition repressed cell cycle process, migration, invasion, epithelial-mesenchymal transition and glycolysis in HCC cells. Mechanistically, circ_0001445 could promote ALX4 expression through targeting miR-942-5p. Moreover, miR-9425p overexpression reversed the inhibitory effect of circ_0001445 on HCC cell progression. The effect of miR-942-5p on HCC cell development was rescued following the elevation of ALX4. In addition, circ_0001445 overexpression restrained tumorigenesis in vivo. In conclusion, circ_0001445 played a negative role in HCC progression by modulating miR942-5p/ALX4 axis, which might provide a novel target for HCC therapy. Keywords ALX4

HCC  Circ_0001445  MiR-942-5p 

Q. Xu  L. Zhou  G. Yang  F. Meng  Y. Wan  L. Wang  L. Zhang (&) Department of Geriatric Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277, Yanta West Road, Xi’an 710061, Shaanxi, China e-mail: [email protected]

Abbreviations CircRNAs Circular RNAs. HCC Hepatocellular carcinoma. ALX4 Aristaless-like homeobox 4. QRT-PCR Quantitative real-time polymerase chain reaction.

Introduction Hepatocellular carcinoma (HCC) mainly occurs in patients with chronic liver disease and cirrhosis (Yang and Roberts 2010). HCC has become the third most common cause of cancer-related mortality in the world (Siegel et al. 2017). Currently, the treatment strategies have made great improvements. However, the overall treatment effect was not significant due to the propensity for metastasis (Hao et al. 2009). Therefore, looking for novel methods for HCC therapy is of great significance. Circular RNAs (circRNAs) are a family of noncoding RNAs (ncRNAs) which possess covalent closed loops (Memczak et al. 2013). It has been reported that circRNAs function as essential regulators in HCC. For example, circ_0056836 contributed to HCC cell motility and growth (Li et al. 2020). Circ_0072309 overexpression repressed tumor cell viability, metastasis and facilitated apoptosis (Yu et al. 2020). These findings suggested that circRNAs played

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different roles in HCC. Circ_0001445 (also termed as circSMARCA5) was demonstrated to serve as a tumor suppressor in HCC (Liu et al. 2019; Zhang et al. 2018). Even so, our understandings on the roles of circ_0001445 remain insufficient. MicroRNAs (miRNAs) are ncRNAs with * 22 nucleotide