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Article

The mechanism of adenosine-mediated activation of lncRNA MEG3 and its antitumor effects in human hepatoma cells

Corrigendum in: /10.3892/ijo.2025.5765
  • Authors:
    • Li-Xuan Liu
    • Wei Deng
    • Xiao-Tao Zhou
    • Rui-Pei Chen
    • Meng-Qi Xiang
    • Yi-Tian Guo
    • Ze-Jin Pu
    • Rui Li
    • Ge-Fei Wang
    • Ling-Fei Wu
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China, Key Laboratory of Infectious Diseases and Immunopathology of Guangdong Province, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China, Department of Microbiology and Immunology, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
  • Pages: 421-429
    |
    Published online on: November 18, 2015
       https://doi.org/10.3892/ijo.2015.3248
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Abstract

Long non-coding RNA MEG3 is suggested to function as a tumor suppressor. However, the activation mechanism of MEG3 is still not well understood and data are not available on its role under adenosine-induced apoptosis. In this study, HepG2 cells were treated with adenosine or 5-Aza‑cdR. Methylation status of MEG3 promoter was detected by methylation specific PCR (MSP) and MEG3 expression was determined by qRT-PCR. PcDNA3.1-MEG3 recombinant plasmid was constructed and transfected to hepatoma HepG2 and Huh7 cells. Cell growth, morphological changes, cell-cycle distribution and apoptosis were analyzed by MTT assay, fluorescence microscopy and flow cytometry. The mRNA and protein expression levels were detected by qRT-PCR and western blot analysis. MEG3 binding proteins were screened by the improved MS2 biotin tagged RNA affinity purification method. The co-expression network of MEG3 was generated by GO analysis and ILF3 was identified as MEG3 binding protein by RNA pulldown and western blot analysis. Both adenosine and 5-Aza-CdR increased MEG3 mRNA expression and the CpG island of MEG3 gene in HepG2 cells was typical hypermethylation. Ectopic expression of MEG3 inhibited hepatoma cell growth in a time-dependent manner, resulted in cell cycle arrest and induced apoptosis. Ectopic expression of MEG3 increased p53, caspase-3 mRNA and protein levels, decreased MDM2 and cyclin D1 mRNA and protein levels, as well as ILF3 protein expression in HepG2 cells. These findings are the first to identify that adenosine increases MEG3 expression by inhibition of DNA methylation and its antitumor effects is involved in MEG3 activation. ILF3 may participate in the anticancer regulation of MEG3 by interacting with MEG3.
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View References

1 

Bosetti C, Turati F and La Vecchia C: Hepatocellular carcinoma epidemiology. Best Pract Res Clin Gastroenterol. 28:753–770. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Ponting CP, Oliver PL and Reik W: Evolution and functions of long noncoding RNAs. Cell. 136:629–641. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Mitra SA, Mitra AP and Triche TJ: A central role for long non-coding RNA in cancer. Front Genet. 3:172012. View Article : Google Scholar : PubMed/NCBI

4 

Qin R, Chen Z, Ding Y, Hao J, Hu J and Guo F: Long non-coding RNA MEG3 inhibits the proliferation of cervical carcinoma cells through the induction of cell cycle arrest and apoptosis. Neoplasma. 60:486–492. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Yang Z, Zhou L, Wu LM, Lai MC, Xie HY, Zhang F and Zheng SS: Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann Surg Oncol. 18:1243–1250. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Miyoshi N, Wagatsuma H, Wakana S, Shiroishi T, Nomura M, Aisaka K, Kohda T, Surani MA, Kaneko-Ishino T and Ishino F: Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q. Genes Cells. 5:211–220. 2000. View Article : Google Scholar : PubMed/NCBI

7 

Zhou Y, Zhong Y, Wang Y, Zhang X, Batista DL, Gejman R, Ansell PJ, Zhao J, Weng C and Klibanski A: Activation of p53 by MEG3 non-coding RNA. J Biol Chem. 282:24731–24742. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Zhou S, Wang J and Zhang Z: An emerging understanding of long noncoding RNAs in kidney cancer. J Cancer Res Clin Oncol. 140:1989–1995. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Zhou Y, Zhang X and Klibanski A: MEG3 noncoding RNA: A tumor suppressor. J Mol Endocrinol. 48:R45–R53. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Zhang X, Zhou Y, Mehta KR, Danila DC, Scolavino S, Johnson SR and Klibanski A: A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells. J Clin Endocrinol Metab. 88:5119–5126. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Jia LF, Wei SB, Gan YH, Guo Y, Gong K, Mitchelson K, Cheng J and Yu GY: Expression, regulation and roles of miR-26a and MEG3 in tongue squamous cell carcinoma. Int J Cancer. 135:2282–2293. 2014. View Article : Google Scholar

12 

Kang W, Seol HJ, Seong DH, Kim J, Kim Y, Kim SU, Nam DH and Joo KM: Adenosine potentiates the therapeutic effects of neural stem cells expressing cytosine deaminase against meta-static brain tumors. Oncol Rep. 30:1101–1106. 2013.PubMed/NCBI

13 

Wu LF, Wei BL, Guo YT, Ye YQ, Li GP, Pu ZJ and Feng JL: Apoptosis induced by adenosine involves endoplasmic reticulum stress in EC109 cells. Int J Mol Med. 30:797–804. 2012.PubMed/NCBI

14 

Wu LF, Ye YQ, Huang GY, Li HB, Li GP, Pu ZJ, Wei BL and Feng JL: Involvement of endoplasmic reticulum stress in adenosine-induced human hepatoma HepG2 cell apoptosis. Oncol Rep. 26:73–79. 2011.PubMed/NCBI

15 

Xiang MQ, Liu LX, De W, Ye YQ, Pu ZJ and Wu LF: The mechanism of demethylation on adenosine and homocysteine-induced apoptosis in HepG2 cells. Chin Pharmacol Bull. 30:973–979. 2014.

16 

Wu LF, Guo YT, Zhang QH, Xiang MQ, Deng W, Ye YQ, Pu ZJ, Feng JL and Huang GY: Enhanced antitumor effects of adenoviral-mediated siRNA against GRP78 gene on adenosine-induced apoptosis in human hepatoma HepG2 cells. Int J Mol Sci. 15:525–544. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Gong C, Popp MW and Maquat LE: Biochemical analysis of long non-coding RNA-containing ribonucleoprotein complexes. Methods. 58:88–93. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Lo PH, Tanikawa C, Katagiri T, Nakamura Y and Matsuda K: Identification of novel epigenetically inactivated gene PAMR1 in breast carcinoma. Oncol Rep. 33:267–273. 2015.

19 

Zhao J, Dahle D, Zhou Y, Zhang X and Klibanski A: Hyper-methylation of the promoter region is associated with the loss of MEG3 gene expression in human pituitary tumors. J Clin Endocrinol Metab. 90:2179–2186. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Zhang X, Gejman R, Mahta A, Zhong Y, Rice KA, Zhou Y, Cheunsuchon P, Louis DN and Klibanski A: Maternally expressed gene 3, an imprinted noncoding RNA gene, is associated with meningioma pathogenesis and progression. Cancer Res. 70:2350–2358. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Gejman R, Batista DL, Zhong Y, Zhou Y, Zhang X, Swearingen B, Stratakis CA, Hedley-Whyte ET and Klibanski A: Selective loss of MEG3 expression and intergenic differentially methylated region hypermethylation in the MEG3/DLK1 locus in human clinically nonfunctioning pituitary adenomas. J Clin Endocrinol Metab. 93:4119–4125. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Benetatos L, Hatzimichael E, Dasoula A, Dranitsaris G, Tsiara S, Syrrou M, Georgiou I and Bourantas KL: CpG methylation analysis of the MEG3 and SNRPN imprinted genes in acute myeloid leukemia and myelodysplastic syndromes. Leuk Res. 34:148–153. 2010. View Article : Google Scholar

23 

Shirali S, Aghaei M, Shabani M, Fathi M, Sohrabi M and Moeinifard M: Adenosine induces cell cycle arrest and apoptosis via cyclin D1/Cdk4 and Bcl-2/Bax pathways in human ovarian cancer cell line OVCAR-3. Tumour Biol. 34:1085–1095. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Shan X, Fu YS, Aziz F, Wang XQ, Yan Q and Liu JW: Ginsenoside Rg3 inhibits melanoma cell proliferation through down-regulation of histone deacetylase 3 (HDAC3) and increase of p53 acetylation. PLoS One. 9:e1154012014. View Article : Google Scholar : PubMed/NCBI

25 

Haupt Y, Maya R, Kazaz A and Oren M: Mdm2 promotes the rapid degradation of p53. Nature. 387:296–299. 1997. View Article : Google Scholar : PubMed/NCBI

26 

Wu X, Bayle JH, Olson D and Levine AJ: The p53-mdm-2 auto-regulatory feedback loop. Genes Dev. 7A:1126–1132. 1993. View Article : Google Scholar

27 

Michael D and Oren M: The p53-Mdm2 module and the ubiquitin system. Semin Cancer Biol. 13:49–58. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Clegg HV, Itahana Y, Itahana K, Ramalingam S and Zhang Y: Mdm2 RING mutation enhances p53 transcriptional activity and p53-p300 interaction. PLoS One. 7:e382122012. View Article : Google Scholar : PubMed/NCBI

29 

Lu KH, Li W, Liu XH, Sun M, Zhang ML, Wu WQ, Xie WP and Hou YY: Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression. BMC Cancer. 13:4612013. View Article : Google Scholar : PubMed/NCBI

30 

Monsalve M, Wu Z, Adelmant G, Puigserver P, Fan M and Spiegelman BM: Direct coupling of transcription and mRNA processing through the thermogenic coactivator PGC-1. Mol Cell. 6:307–316. 2000. View Article : Google Scholar : PubMed/NCBI

31 

Ohno M, Kunimoto M, Nishizuka M, Osada S and Imagawa M: Ku proteins function as corepressors to regulate farnesoid X receptor-mediated gene expression. Biochem Biophys Res Commun. 390:738–742. 2009. View Article : Google Scholar : PubMed/NCBI

32 

Zhu J, Liu S, Ye F, Shen Y, Tie Y, Zhu J, Wei L, Jin Y, Fu H, Wu Y, et al: Long noncoding RNA MEG3 interacts with p53 protein and regulates partial p53 target genes in hepatoma cells. PLoS One. 10:e01397902015. View Article : Google Scholar : PubMed/NCBI

33 

Shamanna RA, Hoque M, Pe'ery T and Mathews MB: Induction of p53, p21 and apoptosis by silencing the NF90/NF45 complex in human papilloma virus-transformed cervical carcinoma cells. Oncogene. 32:5176–5185. 2013. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Liu L, Deng W, Zhou X, Chen R, Xiang M, Guo Y, Pu Z, Li R, Wang G, Wu L, Wu L, et al: The mechanism of adenosine-mediated activation of lncRNA MEG3 and its antitumor effects in human hepatoma cells Corrigendum in /10.3892/ijo.2025.5765. Int J Oncol 48: 421-429, 2016.
APA
Liu, L., Deng, W., Zhou, X., Chen, R., Xiang, M., Guo, Y. ... Wu, L. (2016). The mechanism of adenosine-mediated activation of lncRNA MEG3 and its antitumor effects in human hepatoma cells Corrigendum in /10.3892/ijo.2025.5765. International Journal of Oncology, 48, 421-429. https://doi.org/10.3892/ijo.2015.3248
MLA
Liu, L., Deng, W., Zhou, X., Chen, R., Xiang, M., Guo, Y., Pu, Z., Li, R., Wang, G., Wu, L."The mechanism of adenosine-mediated activation of lncRNA MEG3 and its antitumor effects in human hepatoma cells Corrigendum in /10.3892/ijo.2025.5765". International Journal of Oncology 48.1 (2016): 421-429.
Chicago
Liu, L., Deng, W., Zhou, X., Chen, R., Xiang, M., Guo, Y., Pu, Z., Li, R., Wang, G., Wu, L."The mechanism of adenosine-mediated activation of lncRNA MEG3 and its antitumor effects in human hepatoma cells Corrigendum in /10.3892/ijo.2025.5765". International Journal of Oncology 48, no. 1 (2016): 421-429. https://doi.org/10.3892/ijo.2015.3248
Copy and paste a formatted citation
x
Spandidos Publications style
Liu L, Deng W, Zhou X, Chen R, Xiang M, Guo Y, Pu Z, Li R, Wang G, Wu L, Wu L, et al: The mechanism of adenosine-mediated activation of lncRNA MEG3 and its antitumor effects in human hepatoma cells Corrigendum in /10.3892/ijo.2025.5765. Int J Oncol 48: 421-429, 2016.
APA
Liu, L., Deng, W., Zhou, X., Chen, R., Xiang, M., Guo, Y. ... Wu, L. (2016). The mechanism of adenosine-mediated activation of lncRNA MEG3 and its antitumor effects in human hepatoma cells Corrigendum in /10.3892/ijo.2025.5765. International Journal of Oncology, 48, 421-429. https://doi.org/10.3892/ijo.2015.3248
MLA
Liu, L., Deng, W., Zhou, X., Chen, R., Xiang, M., Guo, Y., Pu, Z., Li, R., Wang, G., Wu, L."The mechanism of adenosine-mediated activation of lncRNA MEG3 and its antitumor effects in human hepatoma cells Corrigendum in /10.3892/ijo.2025.5765". International Journal of Oncology 48.1 (2016): 421-429.
Chicago
Liu, L., Deng, W., Zhou, X., Chen, R., Xiang, M., Guo, Y., Pu, Z., Li, R., Wang, G., Wu, L."The mechanism of adenosine-mediated activation of lncRNA MEG3 and its antitumor effects in human hepatoma cells Corrigendum in /10.3892/ijo.2025.5765". International Journal of Oncology 48, no. 1 (2016): 421-429. https://doi.org/10.3892/ijo.2015.3248
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