Overexpression of CircZNF720 Inhibits Hepatocellular Carcinoma Progression by Regulating MiR-421/MAPK9

Overview

Journal Mol Biotechnol

Publisher Springer

Specialties Biotechnology
Molecular Biology

Date 2023 Dec 30

PMID 38159171

Authors

Feifei Yang

Zhenjuan Zhuang

ChunYing Liu

Fuliang Li

Jingjing Zhou

Affiliations

Soon will be listed here.

Abstract

Hepatocellular carcinoma (HCC) is characterized by high incidence, high death rate and poor long term prognosis. Abnormal expression of circular RNA (circRNA) has been demonstrated to be closely associated with malignant progression of HCC. However, the effect of circZNF720 on HCC is largely incompletely understood. This study sought to explore the effect of circZNF720 on the progression of HCC by CCK-8, transwell, and flow cytometry experiments. The prognosis of circZNF720 on patients was analyzed by Kaplan-Meier curve. Then, the regulatory mechanisms among circZNF720, miR-421, and MAPK9 were identified by qRT-PCR, dual-luciferase reporter assay, and RIP analysis, respectively. The outcomes of this study disclosed that circZNF720 was lowly expressed in HCC, and this low expression was strongly linked with a poor prognosis for HCC patients. Overexpression of circZNF720 inhibited the proliferation, migration, and invasion of cells, and increased the apoptosis of cells. Mechanistic studies revealed that circZNF720 targeted miR-421 and regulated the development of HCC by acting as a sponge for miRNAs. In addition, MAPK9 was a downstream target of miR-421, and circZNF720 introduction hampered HCC progression by upregulating MAPK9 expression through sponging miR-421. In conclusion, circZNF720 restrained HCC progression by targeting miR-421/MAPK9. This study provides a novel target for the treatment of HCC.

References

Chen F, Fang Y, Zhao R, Le J, Zhang B, Huang R . Evolution in medicinal chemistry of sorafenib derivatives for hepatocellular carcinoma. Eur J Med Chem. 2019; 179:916-935. DOI: 10.1016/j.ejmech.2019.06.070. View

Li J, Sun D, Pu W, Wang J, Peng Y . Circular RNAs in Cancer: Biogenesis, Function, and Clinical Significance. Trends Cancer. 2020; 6(4):319-336. DOI: 10.1016/j.trecan.2020.01.012. View

Wei X, Zheng W, Tian P, He Y, Liu H, Peng M . Oncogenic hsa_circ_0091581 promotes the malignancy of HCC cell through blocking miR-526b from degrading c-MYC mRNA. Cell Cycle. 2020; 19(7):817-824. PMC: 7145323. DOI: 10.1080/15384101.2020.1731945. View

Fei Z, Wang Y, Gu Y, Xie R, Hao Q, Jiang Y . CircKIF5B Promotes Hepatocellular Carcinoma Progression by Regulating the miR-192 Family/XIAP Axis. Front Oncol. 2022; 12:916246. PMC: 9281474. DOI: 10.3389/fonc.2022.916246. View

He K, Li W, Guan D, Gong M, Ye S, Fang Z . Regulatory network reconstruction of five essential microRNAs for survival analysis in breast cancer by integrating miRNA and mRNA expression datasets. Funct Integr Genomics. 2019; 19(4):645-658. DOI: 10.1007/s10142-019-00670-7. View

Wan Z, Li X, Luo X, Wang B, Zhou X, Chen A . The miR-590-3p/CFHR3/STAT3 signaling pathway promotes cell proliferation and metastasis in hepatocellular carcinoma. Aging (Albany NY). 2022; 14(14):5783-5799. PMC: 9365569. DOI: 10.18632/aging.204178. View

Liu Z, Zhou Y, Liang G, Ling Y, Tan W, Tan L . Circular RNA hsa_circ_001783 regulates breast cancer progression via sponging miR-200c-3p. Cell Death Dis. 2019; 10(2):55. PMC: 6343010. DOI: 10.1038/s41419-018-1287-1. View

Zhang W, Liu T, Li T, Zhao X . Hsa_circRNA_102002 facilitates metastasis of papillary thyroid cancer through regulating miR-488-3p/HAS2 axis. Cancer Gene Ther. 2020; 28(3-4):279-293. PMC: 8057948. DOI: 10.1038/s41417-020-00218-z. View

Peng S, Yi L, Liao L, Bin Y, Qu W, Hu H . Circ_0008285 knockdown represses tumor development by miR-384/RRM2 axis in hepatocellular carcinoma. Ann Hepatol. 2022; 27(6):100743. DOI: 10.1016/j.aohep.2022.100743. View

10.

Yuan F, Tang Y, Cao M, Ren Y, Li Y, Yang G . Identification of the hsa_circ_0039466/miR-96-5p/FOXO1 regulatory network in hepatocellular carcinoma by whole-transcriptome analysis. Ann Transl Med. 2022; 10(14):769. PMC: 9372669. DOI: 10.21037/atm-22-3147. View

11.

Liu L, Gu M, Ma J, Wang Y, Li M, Wang H . CircGPR137B/miR-4739/FTO feedback loop suppresses tumorigenesis and metastasis of hepatocellular carcinoma. Mol Cancer. 2022; 21(1):149. PMC: 9297645. DOI: 10.1186/s12943-022-01619-4. View

12.

Guria A, Sharma P, Natesan S, Pandi G . Circular RNAs-The Road Less Traveled. Front Mol Biosci. 2020; 6:146. PMC: 6965350. DOI: 10.3389/fmolb.2019.00146. View

13.

Liu Y, Chen S, Zong Z, Guan X, Zhao Y . CircRNA WHSC1 targets the miR-646/NPM1 pathway to promote the development of endometrial cancer. J Cell Mol Med. 2020; 24(12):6898-6907. PMC: 7299690. DOI: 10.1111/jcmm.15346. View

14.

Liu J, Xue N, Guo Y, Niu K, Gao L, Zhang S . CircRNA_100367 regulated the radiation sensitivity of esophageal squamous cell carcinomas through miR-217/Wnt3 pathway. Aging (Albany NY). 2019; 11(24):12412-12427. PMC: 6949088. DOI: 10.18632/aging.102580. View

15.

Hu T, Chen H, Cao M, Guo F, Cheng X, Han Z . MicroRNA-421 inhibits caspase-10 expression and promotes breast cancer progression. Neoplasma. 2018; 65(1):49-54. DOI: 10.4149/neo_2018_170306N159. View

16.

Zhang B, Zhou J . CircSEC24A (hsa_circ_0003528) interference suppresses epithelial-mesenchymal transition of hepatocellular carcinoma cells via miR-421/MMP3 axis. Bioengineered. 2022; 13(4):9049-9062. PMC: 9161912. DOI: 10.1080/21655979.2022.2057761. View

17.

Sun Y, Liu W, Liu T, Feng X, Yang N, Zhou H . Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J Recept Signal Transduct Res. 2015; 35(6):600-4. DOI: 10.3109/10799893.2015.1030412. View

18.

Wang Z, Zhao Y, Wang Y, Zhang Q, Zou Q, Liang F . CircRNF20 aggravates the progression of non-small-cell lung carcinoma by activating MAPK9. Eur Rev Med Pharmacol Sci. 2020; 24(19):9981-9989. DOI: 10.26355/eurrev_202010_23211. View