miR‑374c‑5p regulates PTTG1 and inhibits cell growth and metastasis in hepatocellular carcinoma by regulating epithelial‑mesenchymal transition

Yang,Gang; Xiog,Yongfu; Wang,Guan; Li,Weinan; Tang,Tao; Sun,Ji; Li,Jingdong

doi:10.3892/mmr.2022.12664

miR‑374c‑5p regulates PTTG1 and inhibits cell growth and metastasis in hepatocellular carcinoma by regulating epithelial‑mesenchymal transition

Authors:
- Gang Yang
- Yongfu Xiog
- Guan Wang
- Weinan Li
- Tao Tang
- Ji Sun
- Jingdong Li
View Affiliations

Affiliations: First Clinical Medical College, Jinan University, Tianhe, Guangzhou, Guangdong 510632, P.R. China, Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China, Physical Examination Center, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
Published online on: March 1, 2022 https://doi.org/10.3892/mmr.2022.12664
Article Number: 148
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

A large number of studies have reported that microRNA (miR)‑374c‑5p plays an important role in the occurrence and development of malignant tumors, but there is no research on the role of miR‑374c‑5p in hepatocellular carcinoma (HCC). The aim of the present study was to investigate the role of miR‑374c‑5p in HCC and the underlying molecular mechanism. The expression of miR‑374c‑5p in HCC tissues and HCC cell lines was analyzed via reverse transcription‑quantitative PCR. The association between miR‑374c‑5p and clinical pathology was also analyzed in patients with HCC. Kaplan‑Meier analysis and Cox multivariate analysis were used to evaluate the prognostic significance of miR‑374c‑5p in HCC. The biological functions of miR‑374c‑5p, including cell proliferation, migration and invasion and its potential molecular mechanism were analyzed in vivo and in vitro. In addition, the molecular mechanism of miR‑374c‑5p in HCC was further explored. The results demonstrated that miR‑374c‑5p expression was lower in HCC than in matched adjacent tissue samples. Patients with low expression of miR‑374c‑5p had poor prognosis and short survival time. Overexpression of miR‑374c‑5p inhibited HCC cell proliferation, migration and invasion in vitro. In vivo, it was found that overexpression of miR‑374c‑5p significantly inhibited the growth and proliferation of HCC cells. Dual‑luciferase reporter assays verified that miR‑374c‑5p directly targets the 3'‑untranslated region of pituitary tumor‑transforming 1 (PTTG1) and regulates PTTG1 expression. In general, it was revealed that miR‑374c‑5p regulates the malignant biological behavior of HCC through PTTG1, thereby affecting epithelial‑mesenchymal transition. Thus, miR‑374c‑5p is a potential biological indicator to predict poor prognosis in patients with HCC.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2020. CA Cancer J Clin. 70:7–30. 2020. View Article : Google Scholar : PubMed/NCBI
2	McGlynn KA, Petrick JL and El-Serag HB: Epidemiology of hepatocellular carcinoma. Hepatology. 73 (Suppl 1):S4–S13. 2021. View Article : Google Scholar : PubMed/NCBI
3	Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, Lencioni R, Koike K, Zucman-Rossi J and Finn RS: Hepatocellular carcinoma. Nat Rev Dis Primers. 7:62021. View Article : Google Scholar : PubMed/NCBI
4	Morishita A, Oura K, Tadokoro T, Fujita K, Tani J and Masaki T: MicroRNAs in the pathogenesis of hepatocellular carcinoma: A review. Cancers (Basel). 13:5142021. View Article : Google Scholar : PubMed/NCBI
5	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
6	Hobert O: Gene regulation by transcription factors and microRNAs. Science. 319:1785–1786. 2008. View Article : Google Scholar : PubMed/NCBI
7	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
8	Cohen A, Burgos-Aceves MA and Smith Y: Estrogen repression of microRNA as a potential cause of cancer. Biomed Pharmacother. 78:234–238. 2016. View Article : Google Scholar : PubMed/NCBI
9	Dong LI, Zheng Y, Gao L and Luo X: lncRNA NEAT1 prompts autophagy and apoptosis in MPTP-induced Parkinson's disease by impairing miR-374c-5p. Acta Biochim Biophys Sin (Shanghai). 53:870–882. 2021. View Article : Google Scholar : PubMed/NCBI
10	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
11	Fu H, Zhang Y, Chen Y, Chen J and Chen P: CSN1 facilitates proliferation and migration of hepatocellular carcinoma cells by upregulating cyclin A2 expression. Mol Med Rep. 23:462021.PubMed/NCBI
12	Mullard A: Addressing cancer's grand challenges. Nat Rev Drug Discov. 19:825–826. 2020. View Article : Google Scholar : PubMed/NCBI
13	Puik JR, Meijer LL, Le Large TY, Prado MM, Frampton AE, Kazemier G and Giovannetti E: miRNA profiling for diagnosis, prognosis and stratification of cancer treatment in cholangiocarcinoma. Pharmacogenomics. 18:1343–1358. 2017. View Article : Google Scholar : PubMed/NCBI
14	Esquela-Kerscher A and Slack FJ: Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI
15	Zhang M, Matyunina LV, Walker LD, Chen W, Xiao H, Benigno BB, Wu R and McDonald JF: Evidence for the importance of post-transcriptional regulatory changes in ovarian cancer progression and the contribution of miRNAs. Sci Rep. 7:81712017. View Article : Google Scholar : PubMed/NCBI
16	Perron MP and Provost P: Protein interactions and complexes in human microRNA biogenesis and function. Front Biosci. 13:2537–2547. 2008. View Article : Google Scholar : PubMed/NCBI
17	Oliveto S, Mancino M, Manfrini N and Biffo S: Role of microRNAs in translation regulation and cancer. World J Biol Chem. 8:45–56. 2017. View Article : Google Scholar : PubMed/NCBI
18	He C, Li Z, Chen P, Huang H, Hurst LD and Chen J: Young intragenic miRNAs are less coexpressed with host genes than old ones: Implications of miRNA-host gene coevolution. Nucleic Acids Res. 40:4002–4012. 2012. View Article : Google Scholar : PubMed/NCBI
19	Gao X, Qiao Y, Han D, Zhang Y and Ma N: Enemy or partner: Relationship between intronic micrornas and their host genes. IUBMB Life. 64:835–840. 2012. View Article : Google Scholar : PubMed/NCBI
20	Hinske LC, Galante PA, Kuo WP and Ohno-Machado L: A potential role for intragenic miRNAs on their hosts' interactome. BMC Genomics. 11:5332010. View Article : Google Scholar : PubMed/NCBI
21	Huang Y, Huang H, Li M, Zhang X, Liu Y and Wang Y: MicroRNA-374c-5p regulates the invasion and migration of cervical cancer by acting on the Foxc1/snail pathway. Biomed Pharmacother. 94:1038–1047. 2017. View Article : Google Scholar : PubMed/NCBI
22	Hao S, Tian W, Chen Y, Wang L, Jiang Y, Gao B and Luo D: MicroRNA-374c-5p inhibits the development of breast cancer through TATA-box binding protein associated factor 7-mediated transcriptional regulation of DEP domain containing 1. J Cell Biochem. 120:15360–15368. 2019. View Article : Google Scholar : PubMed/NCBI
23	Yue Y, Deng P, Xiao H, Tan M, Wang H, Tian L, Xie J, Chen M, Luo Y, Wang L, et al: N6-methyladenosine-mediated downregulation of miR-374c-5p promotes cadmium-induced cell proliferation and metastasis by targeting GRM3 in breast cancer cells. Ecotoxicol Environ Saf. 229:1130852022. View Article : Google Scholar : PubMed/NCBI
24	Nieto MA, Huang RY, Jackson RA and Thiery JP: EMT: 2016. Cell. 166:21–45. 2016. View Article : Google Scholar : PubMed/NCBI
25	Pastushenko I and Blanpain C: EMT transition states during tumor progression and metastasis. Trends Cell Biol. 29:212–226. 2019. View Article : Google Scholar : PubMed/NCBI
26	Jayachandran A, Dhungel B and Steel JC: Epithelial-to-mesenchymal plasticity of cancer stem cells: Therapeutic targets in hepatocellular carcinoma. J Hematol Oncol. 9:742016. View Article : Google Scholar : PubMed/NCBI
27	Giannelli G, Koudelkova P, Dituri F and Mikulits W: Role of epithelial to mesenchymal transition in hepatocellular carcinoma. J Hepatol. 65:798–808. 2016. View Article : Google Scholar : PubMed/NCBI
28	Georgakopoulos-Soares I, Chartoumpekis DV, Kyriazopoulou V and Zaravinos A: EMT factors and metabolic pathways in cancer. Front Oncol. 10:4992020. View Article : Google Scholar : PubMed/NCBI
29	Guo XC, Li L, Gao ZH, Zhou HW, Li J and Wang QQ: The long non-coding RNA PTTG3P promotes growth and metastasis of cervical cancer through PTTG1. Aging (Albany NY). 11:1333–1341. 2019. View Article : Google Scholar : PubMed/NCBI
30	Horning AM, Wang Y, Lin CK, Louie AD, Jadhav RR, Hung CN, Wang CM, Lin CL, Kirma NB, Liss MA, et al: Single-Cell RNA-seq reveals a subpopulation of prostate cancer cells with enhanced cell-cycle-related transcription and attenuated androgen response. Cancer Res. 78:853–864. 2018. View Article : Google Scholar : PubMed/NCBI
31	Qiu M, Li G, Wang P, Li X, Lai F, Luo R, Liu B and Lin J: aarF domain containing kinase 5 gene promotes invasion and migration of lung cancer cells through ADCK5-SOX9-PTTG1 pathway. Exp Cell Res. 392:1120022020. View Article : Google Scholar : PubMed/NCBI
32	Parte S, Virant-Klun I, Patankar M, Batra SK, Straughn A and Kakar SS: PTTG1: A unique regulator of stem/cancer stem cells in the ovary and ovarian cancer. Stem Cell Rev Rep. 15:866–879. 2019. View Article : Google Scholar : PubMed/NCBI
33	Ren Q and Jin B: The clinical value and biological function of PTTG1 in colorectal cancer. Biomed Pharmacother. 89:108–115. 2017. View Article : Google Scholar : PubMed/NCBI
34	Meng C, Zou Y, Hong W, Bao C and Jia X: Estrogen-regulated PTTG1 promotes breast cancer progression by regulating cyclin kinase expression. Mol Med. 26:332020. View Article : Google Scholar : PubMed/NCBI