CircWHSC1 serves as an oncogene to promote hepatocellular carcinoma progression

• Published in: European journal of clinical investigation 2021-06, Vol.51 (6), p.e13487-n/a
• Main Authors: Lyu, Pengfei, Zhai, Zhensheng, Hao, Zhengwen, Zhang, Haoruo, He, Jiefeng
• Format: Article
• Language: English
• Subjects: Animals; Assaying; Cancer; Carcinoma, Hepatocellular - genetics; Cell growth; Cell Line, Tumor; Cell migration; Cell proliferation; Cell Proliferation - genetics; Cholecystokinin; circWHSC1; Exosomes; Gene Knockdown Techniques; Hepatocellular carcinoma; Histone-Lysine N-Methyltransferase - genetics; Homeobox; Homeodomain Proteins - genetics; HOXA1; HOXA1 protein; Humans; Immunoprecipitation; Kinases; Liver cancer; Liver Neoplasms - genetics; Metastases; Metastasis; Mice; MicroRNAs - genetics; miR‐142‐3p; Morphology; mRNA; Neoplasm Transplantation; Oncogenes; Polymerase chain reaction; Real-Time Polymerase Chain Reaction; Repressor Proteins - genetics; Ribonucleic acid; RNA; RNA, Circular - genetics; RNA, Messenger; Transcription Factors - genetics; Transmission electron microscopy; Tumorigenesis; Tumors; tumour‐promoting; Xenografts; Xenotransplantation
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/eci.13487

Background Circular RNAs (circRNAs) function as vital regulators in multifarious cancers, including hepatocellular carcinoma (HCC). However, the roles of circRNA Wolf‐Hirschhorn syndrome candidate gene‐1 (circWHSC1) in HCC are barely known. Methods Quantitative real‐time polymerase chain reaction (qRT‐PCR) was conducted for the levels of circWHSC1, miR‐142‐3p, miR‐421, miR‐665 and homeobox A1 (HOXA1) mRNA. Cell Counting Kit‐8 (CCK‐8) assay, colony formation assay and 5′‐ethynyl‐2′‐deoxyuridine (EdU) assay were used to evaluate cell proliferation ability. Transwell assay was adopted for cell migration and invasion. Western blot assay was employed for protein levels. RNA pull‐down assay, dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay were executed to verify the interaction between miR‐142‐3p and circWHSC1 or HOXA1. Murine xenograft model assay was conducted for the role of circWHSC1 in vivo. The morphology of exosomes was observed by transmission electron microscopy (TEM). Results CircWHSC1 was elevated in HCC tissues and cells, and high level of circWHSC1 was associated with worse overall survival of HCC patients. Knockdown of circWHSC1 suppressed HCC cell proliferation and metastasis in vitro and restrained tumorigenesis in vivo. CircWHSC1 functioned as the sponge for miR‐142‐3p, which directly targeted HOXA1. Inhibition of miR‐142‐3p ameliorated the effects of circWHSC1 knockdown on HCC cell proliferation and metastasis. Moreover, miR‐142‐3p overexpression restrained the growth and motility of HCC cells, with HOXA1 elevation reversing the impacts. Additionally, circWHSC1 was increased in HCC patients’ serum and might be a diagnostic indicator for HCC. Conclusion CircWHSC1 played a tumour‐promoting role in HCC by elevating HOXA1 through sponging miR‐142‐3p.