CircFGGY Inhibits Cell Growth, Invasion and Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Regulating the MiR-545-3p/Smad7 Axis

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2022 May 20

PMID 35592246

Authors

Kun-Liang Feng

Na Diao

Zhai-Wen Zhou

Chong-Kai Fang

Ji-Nan Wang

Ying Zhang

Rui Luo

Chong Zhong

Affiliations

Soon will be listed here.

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Circular RNAs (circRNAs) play critical roles in the progression of HCC. However, the role of the newly identified circFGGY (hsa_circ_0006633) in the development and progression of HCC has not been explored. In this study, we found that circFGGY was significantly downregulated in tumor compared with that in adjacent normal liver tissues of patients with HCC. HCC patients with low circFGGY expression had poor overall survival after hepatectomy. Moreover, it was found that circFGGY could inhibit the proliferation, invasion and epithelial-mesenchymal transition of HCC both and . Mechanistically, circFGGY promoted the expression of Smad7, a well-known suppressor of the transforming growth factor-β signaling pathway. In addition, miR-545-3p, a tumor promoter targeting both circFGGY and Smad7, suppressed the upregulation of Smad7 caused by circFGGY overexpression. Collectively, our data revealed that circFGGY inhibits the proliferation and invasion of HCC cells by sponging miR-545-3p and promote the expression of Smad7, indicating that circFGGY functions as a tumor suppressor and could be a prognostic biomarker for HCC.

Citing Articles

Identification and Validation of the Hsa_circ_0001726/miR-140-3p/KRAS Axis in Hepatocellular Carcinoma Based on Microarray Analyses and Experiments.

Chi X, Chen Z, Yu J, Xie X, Lin Z, Chen Y J Clin Transl Hepatol. 2024; 12(11):897-906.

PMID: 39544243 PMC: 11557365. DOI: 10.14218/JCTH.2024.00270.

Current and future perspectives on the regulation and functions of miR-545 in cancer development.

Shen J, Su X, Wang Q, Ke Y, Zheng T, Mao Y Cancer Pathog Ther. 2024; 2(3):142-154.

PMID: 39027151 PMC: 11252520. DOI: 10.1016/j.cpt.2023.09.001.

CircRNAs: Pivotal modulators of TGF-β signalling in cancer pathogenesis.

Bhat A, Gupta G, Dahiya R, Thapa R, Gahtori A, Shahwan M Noncoding RNA Res. 2024; 9(2):277-287.

PMID: 38505309 PMC: 10945146. DOI: 10.1016/j.ncrna.2024.01.013.

The pivotal role of EMT-related noncoding RNAs regulatory axes in hepatocellular carcinoma.

Ghionescu A, Sorop A, Dima S Front Pharmacol. 2023; 14:1270425.

PMID: 37767397 PMC: 10520284. DOI: 10.3389/fphar.2023.1270425.

SMAD Proteins in TGF-β Signalling Pathway in Cancer: Regulatory Mechanisms and Clinical Applications.

Wang Q, Xiong F, Wu G, Wang D, Liu W, Chen J Diagnostics (Basel). 2023; 13(17).

PMID: 37685308 PMC: 10487229. DOI: 10.3390/diagnostics13172769.

References

Wang J, Zhao J, Chu E, Mok M, Go M, Man K . Inhibitory role of Smad7 in hepatocarcinogenesis in mice and in vitro. J Pathol. 2013; 230(4):441-52. DOI: 10.1002/path.4206. View

Jiang Y, Chen X, Zhang W . Overexpression-based detection of translatable circular RNAs is vulnerable to coexistent linear RNA byproducts. Biochem Biophys Res Commun. 2021; 558:189-195. DOI: 10.1016/j.bbrc.2021.04.044. View

Glazar P, Papavasileiou P, Rajewsky N . circBase: a database for circular RNAs. RNA. 2014; 20(11):1666-70. PMC: 4201819. DOI: 10.1261/rna.043687.113. View

Huang G, Liang M, Liu H, Huang J, Li P, Wang C . CircRNA hsa_circRNA_104348 promotes hepatocellular carcinoma progression through modulating miR-187-3p/RTKN2 axis and activating Wnt/β-catenin pathway. Cell Death Dis. 2020; 11(12):1065. PMC: 7734058. DOI: 10.1038/s41419-020-03276-1. View

Changjun L, Feizhou H, Dezhen P, Zhao L, Xianhai M . MiR-545-3p/MT1M axis regulates cell proliferation, invasion and migration in hepatocellular carcinoma. Biomed Pharmacother. 2018; 108:347-354. DOI: 10.1016/j.biopha.2018.09.009. View

Li B, Zhu L, Lu C, Wang C, Wang H, Jin H . circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity. Nat Commun. 2021; 12(1):295. PMC: 7804955. DOI: 10.1038/s41467-020-20527-z. View

Li W, Yang F, Sun C, Huang J, Zhang H, Li X . circPRRC2A promotes angiogenesis and metastasis through epithelial-mesenchymal transition and upregulates TRPM3 in renal cell carcinoma. Theranostics. 2020; 10(10):4395-4409. PMC: 7150475. DOI: 10.7150/thno.43239. View

Lamouille S, Xu J, Derynck R . Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2014; 15(3):178-96. PMC: 4240281. DOI: 10.1038/nrm3758. View

Yu J, Xu Q, Wang Z, Yang Y, Zhang L, Ma J . Circular RNA cSMARCA5 inhibits growth and metastasis in hepatocellular carcinoma. J Hepatol. 2018; 68(6):1214-1227. DOI: 10.1016/j.jhep.2018.01.012. View

10.

Han K, Wang F, Cao C, Ling H, Chen J, Chen R . CircLONP2 enhances colorectal carcinoma invasion and metastasis through modulating the maturation and exosomal dissemination of microRNA-17. Mol Cancer. 2020; 19(1):60. PMC: 7079398. DOI: 10.1186/s12943-020-01184-8. View

11.

Du W, Yang W, Li X, Awan F, Yang Z, Fang L . A circular RNA circ-DNMT1 enhances breast cancer progression by activating autophagy. Oncogene. 2018; 37(44):5829-5842. DOI: 10.1038/s41388-018-0369-y. View

12.

Wu A, Hu Y, Xu Y, Xu J, Wang X, Cai A . Methyltransferase-Like 3-Mediated m6A Methylation of Hsa_circ_0058493 Accelerates Hepatocellular Carcinoma Progression by Binding to YTH Domain-Containing Protein 1. Front Cell Dev Biol. 2021; 9:762588. PMC: 8650312. DOI: 10.3389/fcell.2021.762588. View

13.

Chen R, Chen X, Xia L, Zhang J, Pan Z, Ma X . N-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis. Nat Commun. 2019; 10(1):4695. PMC: 6795808. DOI: 10.1038/s41467-019-12651-2. View

14.

Wang J, Zhou F, Li Y, Li Q, Wu Z, Yu L . Cdc20 overexpression is involved in temozolomide-resistant glioma cells with epithelial-mesenchymal transition. Cell Cycle. 2017; 16(24):2355-2365. PMC: 5788407. DOI: 10.1080/15384101.2017.1388972. View

15.

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

16.

Wu N, Xu J, Du W, Li X, Awan F, Li F . YAP Circular RNA, circYap, Attenuates Cardiac Fibrosis via Binding with Tropomyosin-4 and Gamma-Actin Decreasing Actin Polymerization. Mol Ther. 2020; 29(3):1138-1150. PMC: 7934790. DOI: 10.1016/j.ymthe.2020.12.004. View

17.

Zhang R, Zhang F, Sun Z, Liu P, Zhang X, Ye Y . LINE-1 Retrotransposition Promotes the Development and Progression of Lung Squamous Cell Carcinoma by Disrupting the Tumor-Suppressor Gene FGGY. Cancer Res. 2019; 79(17):4453-4465. DOI: 10.1158/0008-5472.CAN-19-0076. View

18.

Ren Z, Yang Q, Guo J, Huang H, Li B, Yang Z . Circular RNA hsa_circ_0000073 Enhances Osteosarcoma Cells Malignant Behavior by Sponging miR-1252-5p and Modulating CCNE2 and MDM2. Front Cell Dev Biol. 2021; 9:714601. PMC: 8459753. DOI: 10.3389/fcell.2021.714601. View

19.

Kristensen L, Hansen T, Veno M, Kjems J . Circular RNAs in cancer: opportunities and challenges in the field. Oncogene. 2017; 37(5):555-565. PMC: 5799710. DOI: 10.1038/onc.2017.361. View

20.

Du B, Shim J . Targeting Epithelial-Mesenchymal Transition (EMT) to Overcome Drug Resistance in Cancer. Molecules. 2016; 21(7). PMC: 6273543. DOI: 10.3390/molecules21070965. View