Association of single nucleotide polymorphisms in non‑coding RNAs (miRNA‑100 and MALAT1) with susceptibility to hepatitis B virus infection

Talaat,Roba M.; Mady,Amira E.; El-Maadawy,Eman A.; El-Shenawy,Soha Z.; Rizk,Sherine M.; Motawi,Tarek K.

doi:10.3892/ije.2023.18

Association of single nucleotide polymorphisms in non‑coding RNAs (miRNA‑100 and MALAT1) with susceptibility to hepatitis B virus infection

Authors:
- Roba M. Talaat
- Amira E. Mady
- Eman A. El-Maadawy
- Soha Z. El-Shenawy
- Sherine M. Rizk
- Tarek K. Motawi
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Affiliations: Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City (USC), Sadat City, Menoufia Governorate 32958, Egypt, Department of Pharmacy, National Liver Institute, Menoufia University, Menoufia 32958, Egypt, Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City (USC), Sadat City, Menoufia Governorate 32958, Egypt, Department of Clinical Biochemistry and Molecular Diagnostics, National Liver Institute, Menoufia University, Menoufia 32958, Egypt, Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11511, Egypt, Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11511, Egypt
Published online on: July 26, 2023 https://doi.org/10.3892/ije.2023.18
Article Number: 4
Copyright : © Talaat et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

Non‑coding RNAs (ncRNAs) play a vital role in the diagnosis and treatment of hepatitis B virus (HBV). ncRNAs include major classes, such as microRNAs (miRNAs/miRs) and long ncRNAs (lncRNAs). The present study focused on miR‑100 and metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) single nucleotide polymorphisms (SNPs) and their expression levels. In addition to their dual effect on susceptibility to hepatitis B virus (HBV) infection, new molecular biomarkers of HBV infection are suggested. In the present study, 100 patients with HBV infection vs. 100 healthy controls were enrolled. miR‑100 SNP (rs1834306T/C) was detected using the polymerase chain reaction sequence‑specific primers technique, while MALAT1 SNP (rs619586A/G) was detected using the restriction fragment length polymorphism‑PCR technique. Their expression levels were measured using reverse transcription‑quantitative PCR. As per the miR‑100 genotyping results, the TC genotype represented the most frequent genotype in all subjects. However, in MALAT1 SNP, only the dominant AA genotype was detected. A significant upregulation of both miR‑100 (P<0.01) and MALAT1 (P<0.05) expression was observed in the patient group compared to the controls. A positive correlation was found between the viral load and an elevation in miR‑100 and MALAT1 expression levels (r=0.508, P<0.01; and r=0.282, P<0.05, respectively). On the whole, the present study demonstrates that miR‑100 and MALAT1 may be considered as potential molecular markers for the prognosis of patients with HBV infection. To the best of our knowledge, this is the first observational prospective case‑control study to scrutinize all the possible correlations between miR‑100 (rs1834306T/C) and MALAT1 (rs619586A/SNPs) and their expression levels. Further extensive studies with large sample sizes are recommended to confirm the findings obtained herein.

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1	Ezbarami ZT, Hassani P, Tafreshi MZ and Majd HA: A qualitative study on individual experiences of chronic hepatitis B patients. Nurs Open. 4:310–318. 2017.PubMed/NCBI View Article : Google Scholar
2	Asgari S, Chaturvedi N, Scepanovic P, Hammer C, Semmo N, Giostra E, Müllhaupt B, Angus P, Thompson AJ, Moradpour D and Fellay J: Human genomics of acute liver failure due to hepatitis B virus infection: An exome sequencing study in liver transplant recipients. J Viral Hepat. 26:271–277. 2019.PubMed/NCBI View Article : Google Scholar
3	Revill P, Testoni B, Locarnini S and Zoulim F: Global strategies are required to cure and eliminate HBV infection. Nat Rev Gastroenterol Hepatol. 13:239–248. 2016.PubMed/NCBI View Article : Google Scholar
4	Alavi M, Grebely J, Hajarizadeh B, Amin J, Larney S, Law MG, George J, Degenhardt L and Dore GJ: Mortality trends among people with hepatitis B and C: A population-based linkage study, 1993-2012. BMC Infect Dis. 18(215)2018.PubMed/NCBI View Article : Google Scholar
5	Cao MX, Jiang YP, Tang YL and Liang X: The crosstalk between lncRNA and microRNA in cancer metastasis: Orchestrating the epithelial-mesenchymal plasticity. Oncotarget. 8:12472–12483. 2017.PubMed/NCBI View Article : Google Scholar
6	Yamamura S, Imai-Sumida M, Tanaka Y and Dahiya R: Interaction and cross-talk between non-coding RNAs. Cell Mol Life Sci. 75:467–484. 2018.PubMed/NCBI View Article : Google Scholar
7	Tripathi R, Chakraborty P and Varadwaj PK: Unraveling long non-coding RNAs through analysis of high-throughput RNA-sequencing data. Noncoding RNA Res. 2:111–118. 2017.PubMed/NCBI View Article : Google Scholar
8	Bayoumi AS, Sayed A, Broskova Z, Teoh JP, Wilson J, Su H, Tang YL and Kim IM: Crosstalk between long non-coding RNAs and microRNAs in health and disease. Int J Mol Sci. 17(356)2016.PubMed/NCBI View Article : Google Scholar
9	Kohlhapp FJ, Mitra AK, Lengyel E and Peter ME: MicroRNAs as mediators and communicators between cancer cells and the tumor microenvironment. Oncogene. 34:5857–5868. 2015.PubMed/NCBI View Article : Google Scholar
10	Deng K, Wang H, Guo X and Xia J: The crosstalk between long, non-coding RNAs and microRNAs in gastric cancer. Acta Biochim Biophys Sin (Shanghai). 48:111–116. 2015.PubMed/NCBI View Article : Google Scholar
11	Paneru B, Ali A, Al-Tobasei R, Kenney B and Salem M: Crosstalk among lncRNAs, microRNAs and mRNAs in the muscle ‘degradome’ of rainbow trout. Sci Rep. 8(8416)2018.PubMed/NCBI View Article : Google Scholar
12	Qin C, Huang RY and Wang ZX: Potential role of miR-100 in cancer diagnosis, prognosis, and therapy. Tumor Biol. 36:1403–1409. 2015.PubMed/NCBI View Article : Google Scholar
13	Lin Y, Deng W, Pang J, Kemper T, Hu J, Yin J, Zhang J and Lu M: The microRNA-99 family modulates hepatitis B virus replication by promoting IGF-1R/PI3K/Akt/mTOR/ULK1 signaling-induced autophagy. Cell Microbiol. 19:1–15. 2017.PubMed/NCBI View Article : Google Scholar
14	Tan JY and Marques AC: miRNA-mediated crosstalk between transcripts: The missing ‘linc’? Bioessays. 38:295–301. 2016.PubMed/NCBI View Article : Google Scholar
15	He RZ, Luo DX and Mo YY: Emerging roles of lncRNAs in the post-transcriptional regulation in cancer. Genes Dis. 6:6–15. 2019.PubMed/NCBI View Article : Google Scholar
16	Bhat SA, Ahmad SM, Mumtaz PT, Malik AA, Dar MA, Urwat U, Shah RA and Ganai NA: Long non-coding RNAs: Mechanism of action and functional utility. Noncoding RNA Res. 1:43–50. 2016.PubMed/NCBI View Article : Google Scholar
17	Fernandes JCR, Acuña SM, Aoki JI, Floeter-Winter LM and Muxel SM: Long non-coding RNAs in the regulation of gene expression: Physiology and disease. Noncoding RNA. 5(17)2019.PubMed/NCBI View Article : Google Scholar
18	Amodio N, Raimondi L, Juli G, Stamato MA, Caracciolo D, Tagliaferri P and Tassone P: MALAT1: A druggable long non-coding RNA for targeted anti-cancer approaches. J Hematol Oncol. 11(63)2018.PubMed/NCBI View Article : Google Scholar
19	Ren D, Li H, Li R, Sun J, Guo P, Han H, Yang Y and Li J: Novel insight into MALAT-1 in cancer: Therapeutic targets and clinical applications. Oncol Lett. 11:1621–1630. 2016.PubMed/NCBI View Article : Google Scholar
20	Sun Y and Ma L: New insights into long non-coding RNA malat1 in cancer and metastasis. Cancers (Basel). 11(216)2019.PubMed/NCBI View Article : Google Scholar
21	Zhao M, Wang S, Li Q, Ji Q, Guo P and Liu X: Malat1: A long non-coding RNA highly associated with human cancers. Oncol Lett. 16:19–26. 2018.PubMed/NCBI View Article : Google Scholar
22	Fareed M and Afzal M: Single nucleotide polymorphism in genome-wide association of human population: A tool for broad spectrum service. Egypt J Med Hum Genet. 14:123–134. 2013.
23	Castellanos-Rubio A and Ghosh S: Disease-associated SNPs in inflammation-related lncRNAs. Front Immunol. 10(420)2019.PubMed/NCBI View Article : Google Scholar
24	Motawi TK, Mady AE, Shaheen S, Elshenawy SZ, Talaat RM and Rizk SM: Genetic variation in microRNA-100 (miR-100) rs1834306 T/C associated with Hepatitis B virus (HBV) infection: Correlation with expression level. Infect Genet Evol. 73:444–449. 2019.PubMed/NCBI View Article : Google Scholar
25	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta DeltaC(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
26	Fedeli U, Grande E, Grippo F and Frova L: Mortality associated with hepatitis C and hepatitis B virus infection: A nationwide study on multiple causes of death data. World J Gastroenterol. 23:1866–1871. 2017.PubMed/NCBI View Article : Google Scholar
27	Lok AS, Zoulim F, Dusheiko G and Ghany MG: Hepatitis B cure: From discovery to regulatory approval. Hepatology. 66:1296–1313. 2017.PubMed/NCBI View Article : Google Scholar
28	Ahmadi A, Kaviani S, Yaghmaie M, Pashaiefar H, Ahmadvand M, Jalili M, Alimoghaddam K, Eslamijouybari M and Ghavamzadeh A: Altered expression of MALAT 1 lncRNA in chronic lymphocytic leukemia patients, correlation with cytogenetic findings. Blood Res. 53:320–324. 2018.PubMed/NCBI View Article : Google Scholar
29	Frías-Lasserre D and Villagra CA: The importance of ncRNAs as epigenetic mechanisms in phenotypic variation and organic evolution. Front Microbiol. 8(2483)2017.PubMed/NCBI View Article : Google Scholar
30	Wu M, Lin Z, Li X, Xin X, An J, Zheng Q, Yang Y and Lu D: HULC cooperates with MALAT1 to aggravate liver cancer stem cells growth through telomere repeat-binding factor 2. Sci Rep. 6(36045)2016.PubMed/NCBI View Article : Google Scholar
31	Liu Y, Pan S, Liu L, Zhai X, Liu J, Wen J, Zhang Y, Chen J, Shen H and Hu Z: A genetic variant in long non-coding RNA HULC contributes to risk of HBV-related hepatocellular carcinoma in a Chinese population. PLoS One. 7(e35145)2012.PubMed/NCBI View Article : Google Scholar
32	Zhao K, Jin S, Wei B, Cao S and Xiong Z: Association study of genetic variation of lncRNA MALAT1 with carcinogenesis of colorectal cancer. Cancer Manag Res. 10:6257–6261. 2018.PubMed/NCBI View Article : Google Scholar
33	Motawi TMK, El-Maraghy SA, Sabry D and Mehana NA: The expression of long non-coding RNA genes is associated with expression with polymorphisms of HULC rs7763881 and MALAT1 rs619586 in hepatocellular carcinoma and HBV Egyptian patients. J Cell Biochem. 120:14645–14656. 2019.PubMed/NCBI View Article : Google Scholar
34	Yuan LT, Chang JH, Lee HL, Yang YC, Su SC, Lin CL, Yang SF and Chien MH: Genetic variants of lncRNA MALAT1 exert diverse impacts on the risk and clinicopathologic characteristics of patients with hepatocellular carcinoma. J Clin Med. 8(1406)2019.PubMed/NCBI View Article : Google Scholar
35	Wang BG, Xu Q, Lv Z, Fang XX, Ding HX, Wen J and Yuan Y: Association of twelve polymorphisms in three onco-lncRNa genes with hepatocellular cancer risk and prognosis: A case-control study. World J Gastroenterol. 24:2482–2490. 2018.PubMed/NCBI View Article : Google Scholar
36	Gong WJ, Peng JB, Yin JY, Li XP, Zheng W, Xiao L, Tan LM, Xiao D, Chen YX, Li X, et al: Association between well-characterized lung cancer lncRNA polymorphisms and platinum-based chemotherapy toxicity in Chinese patients with lung cancer. Acta Pharmacol Sin. 38:581–590. 2017.PubMed/NCBI View Article : Google Scholar
37	Li Q, Zhu W, Zhang B, Wu Y, Yan S, Yuan Y, Zhang H, Li J, Sun K, Wang H and Yu T: The MALAT1 gene polymorphism and its relationship with the onset of congenital heart disease in Chinese. Biosci Rep. 38(BSR20171381)2018.PubMed/NCBI View Article : Google Scholar
38	Zhu R, Liu X and He Z: Long non-coding RNA H19 and MALAT1 gene variants in patients with ischemic stroke in a northern Chinese Han population. Mol Brain. 11(58)2018.PubMed/NCBI View Article : Google Scholar
39	Wang ML and Liu JX: MALAT1 rs619586 polymorphism functions as a prognostic biomarker in the management of differentiated thyroid carcinoma. J Cell Physiol. 235:1700–1710. 2020.PubMed/NCBI View Article : Google Scholar
40	Che D, Yang Y, Xu Y, Fang Z, Pi L, Fu L, Zhou H, Tan Y, Lu Z, Li L, et al: The lncRNA MALAT1 rs619586 G variant confers decreased susceptibility to recurrent miscarriage. Front Physiol. 10(385)2019.PubMed/NCBI View Article : Google Scholar
41	Konishi H, Ichikawa D, Yamamoto Y, Arita T, Shoda K, Hiramoto H, Hamada J, Itoh H, Fujita Y, Komatsu S, et al: Plasma level of metastasis-associated lung adenocarcinoma transcript 1 is associated with liver damage and predicts development of hepatocellular carcinoma. Cancer Sci. 107:149–154. 2016.PubMed/NCBI View Article : Google Scholar
42	Pan Y, Tong S, Cui R, Fan J, Liu C, Lin Y, Tang J, Xie H, Lin P, Zheng T and Yu X: Long non-coding MALAT1 functions as a competing endogenous RNA to regulate vimentin expression by sponging miR-30a-5p in hepatocellular carcinoma. Cell Physiol Biochem. 50:108–120. 2018.PubMed/NCBI View Article : Google Scholar
43	Zhao ZB, Chen F and Bai XF: Long non-coding RNA MALAT1 regulates hepatocellular carcinoma growth under hypoxia via sponging microRNA-200a. Yonsei Med J. 60:727–734. 2019.PubMed/NCBI View Article : Google Scholar
44	Wang Z, Katsaros D, Biglia N, Shen Y, Fu Y, Loo LWM, Jia W, Obata Y and Yu H: High expression of long non-coding RNA MALAT1 in breast cancer is associated with poor relapse-free survival. Breast Cancer Res Treat. 171:261–271. 2018.PubMed/NCBI View Article : Google Scholar
45	Zhu K, Ren Q and Zhao Y: . LncRNA MALAT1 overexpression promotes proliferation, migration and invasion of gastric cancer by activating the PI3K/AKT pathway. Oncol Lett. 17:5335–5342. 2019.PubMed/NCBI View Article : Google Scholar
46	Toraih EA, Ellawindy A, Fala SY, Al Ageeli E, Gouda NS, Fawzy MS and Hosny S: Oncogenic long non-coding RNA MALAT1 and HCV-related hepatocellular carcinoma. Biomed Pharmacother. 102:653–669. 2018.PubMed/NCBI View Article : Google Scholar
47	Wang X, Li M, Wang Z, Han S, Tang X, Ge Y, Zhou L, Zhou C, Yuan Q and Yang M: Silencing of long non-coding RNA MALAT1 by miR-101 and miR-217 inhibits proliferation, migration, and invasion of esophageal squamous cell carcinoma cells. J Biol Chem. 290:3925–3935. 2015.PubMed/NCBI View Article : Google Scholar
48	Liu D, Zhu Y, Pang J, Weng X, Feng X and Guo Y: Knockdown of long non-coding RNA MALAT1 inhibits growth and motility of human hepatoma cells via modulation of miR-195. J Cell Biochem. 119:1368–1380. 2018.PubMed/NCBI View Article : Google Scholar