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miR‑146b‑5p activation of hepatic stellate cells contributes to the progression of fibrosis by directly targeting HIPK1

  • Authors:
    • Junfeng Xie
    • Na Cheng
    • Zhanchao Huang
    • Xu Shu
    • Tianxin Xiang
  • View Affiliations / Copyright

    Affiliations: Department of Hospital Infection Control, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, P.R. China, Department of Infectious Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, P.R. China
    Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 537
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    Published online on: June 27, 2022
       https://doi.org/10.3892/etm.2022.11474
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Abstract

The present study aimed to explore the biological functions of microRNA (miR)‑146b‑5p and homeodomain interacting protein kinase 1 (HIPK1) in the progression of hepatic fibrosis (HF) and to identify the underlying mechanism. A rat HF model was established by administering a subcutaneous injection of carbon tetrachloride (CCl4). Relative levels of miR‑146b‑5p and HIPK1 in fibrotic rat liver tissues and the rat hepatic stellate cell (HSC) line HSC‑T6 were measured by quantitative reverse transcription PCR, western blotting and immunohistochemistry. Following activation of HSC‑T6 cells by lipopolysaccharide (LPS) induction, cell viability was examined by MTT assay. Transfection of miR‑146b‑5p mimic or inhibitor into HSC‑T6 cells was performed, with the aim to identify the influence of miR‑146b‑5p on HSC‑T6 cell behavior. The targeting relationship between miR‑146b‑5p and HIPK1 was predicted by TargetScan 7.2 and StarBase 3.0 and it was later verified by a dual‑luciferase reporter assay. Through lentivirus transfection, the biological function of HIPK1 in regulating the progression of HF and the underlying mechanism were investigated. The results showed that miR‑146b‑5p was upregulated in liver tissues of rats with HF and activated HSC‑T6 cells, while HIPK1 was downregulated in liver tissues of rats with HF and activated HSC‑T6 cells. miR‑146b‑5p was able to upregulate the activation markers of LPS‑induced HSC‑T6 cells, upregulate COL1A1 and TGF‑β, increase cell viability and contribute to fibrosis progression. HIPK1 was validated as the direct target of miR‑146b‑5p and its overexpression could effectively reduce the effect of miR‑146b‑5p in contribution to the progression of HF. In conclusion, miR‑146b‑5p was significantly upregulated during the progression of HF. By targeting and downregulating HIPK1, miR‑146b‑5p could significantly activate HSCs, upregulate COL1A1 and TGF‑β and contribute to fibrosis progression. miR‑146b‑5p is a potential biomarker and therapeutic target for HF.
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1 

Hernandez-Gea V and Friedman SL: Pathogenesis of liver fibrosis. Annu Rev Pathol. 6:425–456. 2011.PubMed/NCBI View Article : Google Scholar

2 

Hou W and Syn WK: Role of metabolism in hepatic stellate cell activation and fibrogenesis. Front Cell Dev Biol. 6(150)2018.PubMed/NCBI View Article : Google Scholar

3 

Lee UE and Friedman SL: Mechanisms of hepatic fibrogenesis. Best Pract Res Clin Gastroenterol. 25:195–206. 2011.PubMed/NCBI View Article : Google Scholar

4 

Jung YK and Yim HJ: Reversal of liver cirrhosis: Current evidence and expectations. Korean J Intern Med. 32:213–228. 2017.PubMed/NCBI View Article : Google Scholar

5 

Mekala S, Tulimilli SV, Geesala R, Manupati K, Dhoke NR and Das A: Cellular crosstalk mediated by platelet-derived growth factor BB and transforming growth factor beta during hepatic injury activates hepatic stellate cells. Can J Physiol Pharmacol. 96:728–741. 2018.PubMed/NCBI View Article : Google Scholar

6 

Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004.PubMed/NCBI View Article : Google Scholar

7 

Nakamura M, Kanda T, Sasaki R, Haga Y, Jiang X, Wu S, Nakamoto S and Yokosuka O: MicroRNA-122 inhibits the production of inflammatory cytokines by targeting the PKR activator PACT in human hepatic stellate cells. PLoS One. 10(e0144295)2015.PubMed/NCBI View Article : Google Scholar

8 

Yu F, Chen B, Fan X, Li G, Dong P and Zheng J: Epigenetically-regulated MicroRNA-9-5p suppresses the activation of hepatic stellate cells via TGFBR1 and TGFBR2. Cell Physiol Biochem. 43:2242–2252. 2017.PubMed/NCBI View Article : Google Scholar

9 

Li X, Luo Y, Yu L, Lin Y, Luo D, Zhang H, He Y, Kim YO, Kim Y, Tang S and Min W: SENP1 mediates TNF-induced desumoylation and cytoplasmic translocation of HIPK1 to enhance ASK1-dependent apoptosis. Cell Death Differ. 15:739–750. 2008.PubMed/NCBI View Article : Google Scholar

10 

Rey C, Soubeyran I, Mahouche I, Pedeboscq S, Bessede A, Ichas F, De Giorgi F and Lartigue L: HIPK1 drives p53 activation to limit colorectal cancer cell growth. Cell Cycle. 12:1879–1891. 2013.PubMed/NCBI View Article : Google Scholar

11 

van der Laden J, Soppa U and Becker W: Effect of tyrosine autophosphorylation on catalytic activity and subcellular localisation of homeodomain-interacting protein kinases (HIPK). Cell Commun Signal. 13(3)2015.PubMed/NCBI View Article : Google Scholar

12 

Kondo S, Lu Y, Debbas M, Lin AW, Sarosi I, Itie A, Wakeham A, Tuan J, Saris C, Elliott G, et al: Characterization of cells and gene-targeted mice deficient for the p53-binding kinase homeodomain-interacting protein kinase 1 (HIPK1). Proc Natl Acad Sci USA. 100:5431–5436. 2003.PubMed/NCBI View Article : Google Scholar

13 

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.PubMed/NCBI View Article : Google Scholar

14 

Kisseleva T and Brenner DA: Mechanisms of fibrogenesis. Exp Biol Med (Maywood). 233:109–122. 2008.PubMed/NCBI View Article : Google Scholar

15 

Iwaisako K, Jiang C, Zhang M, Cong M, Moore-Morris TJ, Park TJ, Liu X, Xu J, Wang P, Paik YH, et al: Origin of myofibroblasts in the fibrotic liver in mice. Proc Natl Acad Sci USA. 111:E3297–E3305. 2014.PubMed/NCBI View Article : Google Scholar

16 

Jesudian A, Desale S, Julia J, Landry E, Maxwell C, Kallakury B, Laurin J and Shetty K: Donor factors including donor risk index predict fibrosis progression, allograft loss, and patient survival following liver transplantation for hepatitis C virus. J Clin Exp Hepatol. 6:109–114. 2016.PubMed/NCBI View Article : Google Scholar

17 

Winkle M, El-Daly SM, Fabbri M and Calin GA: Noncoding RNA therapeutics-challenges and potential solutions. Nat Rev Drug Discov. 20:629–651. 2021.PubMed/NCBI View Article : Google Scholar

18 

Ali Sheikh MS, Alduraywish A, Almaeen A, Alruwali M, Alruwaili R, Alomair BM, Salma U, Hedeab GM, Bugti N and Abdulhabeeb IAM: Therapeutic value of miRNAs in coronary artery disease. Oxid Med Cell Longev. 2021(8853748)2021.PubMed/NCBI View Article : Google Scholar

19 

Fodor A, Lazar AL, Buchman C, Tiperciuc B, Orasan OH and Cozma A: MicroRNAs: The link between the metabolic syndrome and oncogenesis. Int J Mol Sci. 22(6337)2021.PubMed/NCBI View Article : Google Scholar

20 

Riaz F, Chen Q, Lu K, Osoro EK, Wu L, Feng L, Zhao R, Yang L, Zhou Y, He Y, et al: Inhibition of miR-188-5p alleviates hepatic fibrosis by significantly reducing the activation and proliferation of HSCs through PTEN/PI3K/AKT pathway. J Cell Mol Med. 25:4073–4087. 2021.PubMed/NCBI View Article : Google Scholar

21 

Li B, Liu J, Xin X, Zhang L, Zhou J, Xia C, Zhu W and Yu H: MiR-34c promotes hepatic stellate cell activation and liver fibrogenesis by suppressing ACSL1 expression. Int J Med Sci. 18:615–625. 2021.PubMed/NCBI View Article : Google Scholar

22 

Li H, Zhang L, Cai N, Zhang B and Sun S: MicroRNA-494-3p prevents liver fibrosis and attenuates hepatic stellate cell activation by inhibiting proliferation and inducing apoptosis through targeting TRAF3. Ann Hepatol. 23(100305)2021.PubMed/NCBI View Article : Google Scholar

23 

Zhou M, Gao Y, Wang M, Guo X, Li X, Zhu F, Xu S and Qin R: MiR-146b-3p regulates proliferation of pancreatic cancer cells with stem cell-like properties by targeting MAP3K10. J Cancer. 12:3726–3740. 2021.PubMed/NCBI View Article : Google Scholar

24 

Wang D, Feng M, Ma X, Tao K and Wang G: Transcription factor SP1-induced microRNA-146b-3p facilitates the progression and metastasis of colorectal cancer via regulating FAM107A. Life Sci. 277(119398)2021.PubMed/NCBI View Article : Google Scholar

25 

Liu X, Fu Q, Bian X, Fu Y, Xin J, Liang N, Li S, Zhao Y, Fang L, Li C, et al: Long non-coding RNA MAPK8IP1P2 inhibits lymphatic metastasis of thyroid cancer by activating hippo signaling via sponging miR-146b-3p. Front Oncol. 10(600927)2021.PubMed/NCBI View Article : Google Scholar

26 

Ouyang B, Pan N, Zhang H, Xing C and Ji W: miR146b5p inhibits tumorigenesis and metastasis of gallbladder cancer by targeting Tolllike receptor 4 via the nuclear factor-κB pathway. Oncol Rep. 45(15)2021.PubMed/NCBI View Article : Google Scholar

27 

Ge S, Wu X, Xiong Y, Xie J, Liu F, Zhang W, Yang L, Zhang S, Lai L, Huang J, et al: HMGB1 inhibits HNF1A to modulate liver fibrogenesis via p65/miR-146b signaling. DNA Cell Biol. 39:1711–1722. 2020.PubMed/NCBI View Article : Google Scholar

28 

Ge S, Zhang L, Xie J, Liu F, He J, He J, Wang X and Xiang T: MicroRNA-146b regulates hepatic stellate cell activation via targeting of KLF4. Ann Hepatol. 15:918–928. 2016.PubMed/NCBI View Article : Google Scholar

29 

Kim YH, Choi CY, Lee SJ, Conti MA and Kim Y: Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors. J Biol Chem. 273:25875–25879. 1998.PubMed/NCBI View Article : Google Scholar

30 

Meng L, Zhao X and Zhang H: HIPK1 interference attenuates inflammation and oxidative stress of acute lung injury via autophagy. Med Sci Monit. 25:827–835. 2019.PubMed/NCBI View Article : Google Scholar

31 

Palkina N, Komina A, Aksenenko M, Moshev A, Savchenko A and Ruksha T: miR-204-5p and miR-3065-5p exert antitumor effects on melanoma cells. Oncol Lett. 15:8269–8280. 2018.PubMed/NCBI View Article : Google Scholar

32 

Conte A and Pierantoni GM: Update on the regulation of HIPK1, HIPK2 and HIPK3 protein kinases by microRNAs. MicroRNA. 7:178–186. 2018.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Xie J, Cheng N, Huang Z, Shu X and Xiang T: miR‑146b‑5p activation of hepatic stellate cells contributes to the progression of fibrosis by directly targeting HIPK1. Exp Ther Med 24: 537, 2022.
APA
Xie, J., Cheng, N., Huang, Z., Shu, X., & Xiang, T. (2022). miR‑146b‑5p activation of hepatic stellate cells contributes to the progression of fibrosis by directly targeting HIPK1. Experimental and Therapeutic Medicine, 24, 537. https://doi.org/10.3892/etm.2022.11474
MLA
Xie, J., Cheng, N., Huang, Z., Shu, X., Xiang, T."miR‑146b‑5p activation of hepatic stellate cells contributes to the progression of fibrosis by directly targeting HIPK1". Experimental and Therapeutic Medicine 24.2 (2022): 537.
Chicago
Xie, J., Cheng, N., Huang, Z., Shu, X., Xiang, T."miR‑146b‑5p activation of hepatic stellate cells contributes to the progression of fibrosis by directly targeting HIPK1". Experimental and Therapeutic Medicine 24, no. 2 (2022): 537. https://doi.org/10.3892/etm.2022.11474
Copy and paste a formatted citation
x
Spandidos Publications style
Xie J, Cheng N, Huang Z, Shu X and Xiang T: miR‑146b‑5p activation of hepatic stellate cells contributes to the progression of fibrosis by directly targeting HIPK1. Exp Ther Med 24: 537, 2022.
APA
Xie, J., Cheng, N., Huang, Z., Shu, X., & Xiang, T. (2022). miR‑146b‑5p activation of hepatic stellate cells contributes to the progression of fibrosis by directly targeting HIPK1. Experimental and Therapeutic Medicine, 24, 537. https://doi.org/10.3892/etm.2022.11474
MLA
Xie, J., Cheng, N., Huang, Z., Shu, X., Xiang, T."miR‑146b‑5p activation of hepatic stellate cells contributes to the progression of fibrosis by directly targeting HIPK1". Experimental and Therapeutic Medicine 24.2 (2022): 537.
Chicago
Xie, J., Cheng, N., Huang, Z., Shu, X., Xiang, T."miR‑146b‑5p activation of hepatic stellate cells contributes to the progression of fibrosis by directly targeting HIPK1". Experimental and Therapeutic Medicine 24, no. 2 (2022): 537. https://doi.org/10.3892/etm.2022.11474
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