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Knockdown of UCA1 attenuated the progression of alcoholic fatty disease by sponging miR-214

Abstract

Alcoholic fatty liver (AFL) is the initial manifestation of Alcoholic liver disease which can develop into alcoholic cirrhosis even extensive necrosis of liver cells, which induces liver failure finally. This study aims to focus on the role of long noncoding RNA UCA1 in AFL and further explored possible mechanism of this disease. We first downloaded GSE28619 to identify the expression of UCA1 in patients with AFL and use lncRNAs microarray to confirm UCA1 expression in serum of patients with AFL. Then we established ethanol-induced L02 cell model to mimic hepatocyte injury condition. By conducting qRT-PCR, we measured the expression of LncRNA UCA1 and miR-214 in serum of patients and ethanol-induced L02 cell. MTT assay, transwell migration, ELISA, qRT-PCR, and western blotting analysis were applied to evaluating the effect of UCA1 on ethanol-induced L02 cell. The bioinformatics analysis and the rescue experiment were devoted to the underlying mechanism. In this study, we first detected the expression of UCA1 was up-regulated in serum of patients with AFL and ethanol-induced L02 cells. And knockdown of UCA1 reversed the inhibiting effect of ethanol on the biological behavior of L02 cells including cell proliferation, migration, and apoptosis. Besides, lncRNA UCA1 regulated the expression of KLF5 by sponging miR-214. LncRNA UCA1 regulated the biological behavior of ethanol-induced L02 cells by sponging miR-214, which may provide novel therapeutic strategies for alcoholic fatty liver.

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References

  • Cai L, Tu L, Li T, Yang X, Ren Y, Gu R, Zhang Q, Yao H, Qu X, Wang Q, Tian J (2019) Downregulation of lncRNA UCA1 ameliorates the damage of dopaminergic neurons, reduces oxidative stress and inflammation in Parkinson’s disease through the inhibition of the PI3K/Akt signaling pathway. Int Immunopharmacol 75:105734

    CAS  Article  Google Scholar 

  • Choudhary NS, Duseja A (2021) Genetic and epigenetic disease modifiers: non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). Transl Gastroenterol Hepatol 6:2

    Article  Google Scholar 

  • Del Campo JA, Gallego P, Grande L (2018) Role of inflammatory response in liver diseases: therapeutic strategies. World J Hepatol 10:1–7

    Article  Google Scholar 

  • Huang X, Gao Y, Qin J, Lu S (2018) lncRNA MIAT promotes proliferation and invasion of HCC cells via sponging miR-214. Am J Physiol Gastrointest Liver Physiol 314:G559–G565

    CAS  Article  Google Scholar 

  • Kakino S, Ohki T, Nakayama H, Yuan X, Otabe S, Hashinaga T, Wada N, Kurita Y, Tanaka K, Hara K, Soejima E, Tajiri Y, Yamada K (2018) Pivotal role of TNF-alpha in the development and progression of nonalcoholic fatty liver disease in a murine model. Horm Metab Res 50:80–87

    CAS  Article  Google Scholar 

  • Klop B, do Rego AT, Cabezas MC (2013) Alcohol and plasma triglycerides. Curr Opin Lipidol 24:321–326

    CAS  Article  Google Scholar 

  • Kong LZ, Chandimali N, Han YH, Lee DH, Kim JS, Kim SU, Kim TD, Jeong DK, Sun HN, Lee DS, Kwon T (2019) Pathogenesis, early diagnosis, and therapeutic management of alcoholic liver disease. Int J Mol Sci 20

  • Krol J, Loedige I, Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11:597–610

    CAS  Article  Google Scholar 

  • Lin CJ, Hu ZG, Yuan GD, Lei B, He SQ (2018) Complements are involved in alcoholic fatty liver disease, hepatitis and fibrosis. World J Hepatol 10:662–669

    Article  Google Scholar 

  • Liu Y, Guo B, Aguilera-Jimenez E, Chu VS, Zhou J, Wu Z, Francis JM, Yang X, Choi PS, Bailey SD, Zhang X (2020) Chromatin looping shapes KLF5-dependent transcriptional programs in human epithelial cancers. Cancer Res 80:5464–5477

    CAS  Article  Google Scholar 

  • Mattick JS, Rinn JL (2015) Discovery and annotation of long noncoding RNAs. Nat Struct Mol Biol 22:5–7

    CAS  Article  Google Scholar 

  • Meroni M, Longo M, Rametta R, Dongiovanni P (2018) Genetic and epigenetic modifiers of alcoholic liver disease. Int J Mol Sci 19

  • Pan W, Li W, Zhao J, Huang Z, Chen S, Wang C, Xue Y, Huang F, Fang Q, Wang J, Brand D, Zheng SG (2019) lncRNA-PDPK2P promotes hepatocellular carcinoma progression through the PDK1/AKT/Caspase 3 pathway. Mol Oncol 13:2246–2258

    CAS  Article  Google Scholar 

  • Qin LT, Tang RX, Lin P, Li Q, Yang H, Luo DZ, Chen G, He Y, Li P (2018) Biological function of UCA1 in hepatocellular carcinoma and its clinical significance: investigation with in vitro and meta-analysis. Pathol Res Pract 214:1260–1272

    CAS  Article  Google Scholar 

  • Rehm J, Samokhvalov AV, Shield KD (2013) Global burden of alcoholic liver diseases. J Hepatol 59:160–168

    Article  Google Scholar 

  • Ren F, Ren JH, Song CL, Tan M, Yu HB, Zhou YJ, Qin YP, Cheng ST, Zhang Y, Huang AL, Chen J, Yang X (2020) LncRNA HOTAIR modulates hepatitis B virus transcription and replication by enhancing SP1 transcription factor. Clin Sci 134:3007–3022

    CAS  Article  Google Scholar 

  • Ren B, Song Z, Chen L, Niu X, Feng Q (2021) Long non-coding RNA UCA1 correlates with elevated disease severity, Th17 cell proportion, inflammatory cytokines, and worse prognosis in acute ischemic stroke patients. J Clin Lab Anal 35:e23697

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rigoutsos I, Furnari F (2010) Gene-expression forum: decoy for microRNAs. Nature 465:1016–1017

    CAS  Article  Google Scholar 

  • Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3:1101–1108

    CAS  Article  Google Scholar 

  • Singal AK, Bataller R, Ahn J, Kamath PS, Shah VH (2018) ACG Clinical Guideline: Alcoholic Liver Disease. Am J Gastroenterol 113:175–194

    Article  Google Scholar 

  • Smekalova EM, Kotelevtsev YV, Leboeuf D, Shcherbinina EY, Fefilova AS, Zatsepin TS, Koteliansky V (2016) lncRNA in the liver: prospects for fundamental research and therapy by RNA interference. Biochimie 131:159–172

    CAS  Article  Google Scholar 

  • Sugimoto K, Takei Y (2017) Pathogenesis of alcoholic liver disease. Hepatol Res 47:70–79

    Article  Google Scholar 

  • Tay Y, Rinn J, Pandolfi PP (2014) The multilayered complexity of ceRNA crosstalk and competition. Nature 505:344–352

    CAS  Article  Google Scholar 

  • Tilg H, Moschen AR, Szabo G (2016) Interleukin-1 and inflammasomes in alcoholic liver disease/acute alcoholic hepatitis and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Hepatology 64:955–965

    CAS  Article  Google Scholar 

  • Vinolo MA, Rodrigues HG, Nachbar RT, Curi R (2011) Regulation of inflammation by short chain fatty acids. Nutrients 3:858–876

    CAS  Article  Google Scholar 

  • Wang KC, Chang HY (2011) Molecular mechanisms of long noncoding RNAs. Mol Cell 43:904–914

    CAS  Article  Google Scholar 

  • Wang F, Ge J, Huang S, Zhou C, Sun Z, Song Y, Xu Y, Ji Y (2021) KLF5/LINC00346/miR148a3p axis regulates inflammation and endothelial cell injury in atherosclerosis. Int J Mol Med 48

  • Xue M, Chen W, Li X (2016) Urothelial cancer associated 1: a long noncoding RNA with a crucial role in cancer. J Cancer Res Clin Oncol 142:1407–1419

    Article  Google Scholar 

  • Yang H, Li Q, Zhang L, Zhu M, Niu J, Xue F, Yang L, Qu Q, Lao Y, Ding Z, Xiao C, Wang K (2020) LncPRYP4-3 serves as a novel diagnostic biomarker for dissecting subtypes of metabolic associated fatty liver disease by targeting RPS4Y2. Clin Exp Med 20:587–600

    Article  Google Scholar 

  • Yang Y, Zhao Z, Hou N, Li Y, Wang X, Wu F, Sun R, Han J, Sun H, Song T, Huang C, Shao Y (2017) MicroRNA214 targets Wnt3a to suppress liver cancer cell proliferation. Mol Med Rep 16:6920–6927

    CAS  Article  Google Scholar 

  • You M, Arteel GE (2019) Effect of ethanol on lipid metabolism. J Hepatol 70:237–248

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This work was supported by National Natural Science Foundation of China (N0.81860431), National Natural Science Foundation of China (N0. 82060447) and Key research and development project of Jiangxi Province (20203BBGL73200)

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Correspondence to Linquan Wu.

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Xiang, H., Tu, B., Luo, M. et al. Knockdown of UCA1 attenuated the progression of alcoholic fatty disease by sponging miR-214. Mamm Genome 33, 534–542 (2022). https://doi.org/10.1007/s00335-022-09953-0

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  • DOI: https://doi.org/10.1007/s00335-022-09953-0