Hsa_circ_0079875 functions as a competitive endogenous RNA to promote hepatocellular carcinoma progression

ABSTRACT

Circular RNA (circRNA) can influence the development of hepatocellular carcinoma (HCC) as a competitive endogenous RNA (ceRNA). However, there are still many circRNAs whose functions are unknown. Our research explores the role of a novel circRNA, hsa_circ_0079875, in HCC. The expression of hsa_circ_0079875 in HCC was verified by next-generation sequencing, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and fluorescence in situ hybridization (FISH). The distribution of hsa_circ_0079875 in HCC cells was investigated by RNA subcellular isolation and FISH assays. The functional effects on HCC proliferation, invasion, migration, cell cycle, and apoptosis were verified by overexpression and knockdown of hsa_circ_0079875. Moreover, xenograft mouse models and immunohistochemistry experiments were used to assess the function of hsa_circ_0079875 in vivo. Hsa_circ_0079875 was up-regulated in HCC tissues and mainly distributed in the cytoplasm. Higher hsa_circ_0079875 leads to larger tumor tissue, more microvascular invasion(MVI) and higher AFP levels, which in turn leads to a poor prognosis. Overexpression of hsa_circ_0079875 can promote the proliferation, migration, and invasion of HCC cells and inhibit apoptosis in vitro and in vivo. Knocking down hsa_circ_0079875 has the opposite effect. Sequencing and biological information predicted the target miRNA and mRNA of hsa_circ_0079875. Further bioinformatics and clinical correlation analysis revealed that hsa_circ_0079875 promote the malignant biological behaviors of HCC through hsa_circ_0079875/miR-519d-59/NRAS ceRNA net. Therefore, hsa_circ_0079875 can be a potential prognostic marker and therapeutic target for HCC.

KEYWORDS:

• Hsa_circ_0079875
• ceRNA net
• hepatocellular carcinoma

Acknowledgements

We thank the Animal Center of Nantong University and the Institute of Liver Diseases of Nantong Third People’s Hospital for providing the experimental platform.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Yicun Liu performed the main part of the study and wrote the original draft. Xi Luo performed the main part of the study. WeiJie Chen, Zhixing Dong and Tiaochun Cheng provided technical support and analyzed the data. Lin Chen, Linling Ju and Weihua Cai contributed to part of the experiments. Zhaolian Bian designed the study, performed the main part, and guided the manuscript writing.

Supplemental material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15384101.2024.2345469

Additional information

Funding

This study was supported by grants from the Science and Technology Bureau (MS22018007), Six Peak Talents in Jiangsu Province (YY-177), Project of Jiangsu Province Youth Medical Talent Development (QNRC2016400), Project of Nantong Youth Medical Talent Development (No.05), Youth Fund of Natural Science Foundation of Jiangsu Province (BK20200965), Scientific Research Fund of Nantong Health Commission (MB2020037), and Health Bureau of Nantong City (grant No. MB2021057). However, the funding sources had no involvement in the study design, collection, analysis, interpretation of data, writing of the report, or the decision to submit the paper for publication.