Open Access

Effect of lincRNA-p21 targeting HIF-1α on biological functions of liver cancer cells

  • Authors:
    • Yibiao Ye
    • Yaorong Peng
    • Yanshan Li
    • Chunxia Liu
    • Yunxiuxiu Xu
    • Wenbin Li
  • View Affiliations

  • Published online on: March 28, 2019     https://doi.org/10.3892/ol.2019.10195
  • Pages: 4964-4968
  • Copyright: © Ye 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: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The effects of long intergenic non-coding ribonucleic acid (lincRNA)-p21 targeting hypoxia-inducible factor-1α (HIF-1α) on proliferation, apoptosis and migration of liver cancer cells were investigated. MHCC97H liver cancer cells were infected with control lentivirus (control group) and lincRNA-p21 lentivirus (observation group), and control stable cell lines and lincRNA-p21 stable cell lines were screened and obtained by using puromycin. The expression levels of lincRNA-p21 messenger RNA (mRNA) in the control and observation groups were analyzed via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Bioinformatics was used to search for the lincRNA-p21 target. The expression of target gene was analyzed via western blotting, and the proliferation, apoptosis, migration and in vivo tumor formation of MHCC97H cells in the control and observation groups were also analyzed. Compared with that in control group, the lincRNA-p21 mRNA level in observation group was increased significantly (P<0.05). It was found via bioinformatic comparison that HIF-1α was one of the targets of lincRNA-p21. Results of Western blotting revealed that the expression level of HIF-1α protein in cells in observation group was significantly downregulated (P<0.05). Besides, the level of vascular endothelial growth factor (VEGF) protein in cells in control group was obviously higher than that in observation group (P<0.05). Compared with those in control group, the cell proliferation and migration capacities in observation group were markedly reduced, but the apoptosis level was significantly increased (P<0.05). According to the in vivo tumor formation assay, the cell proliferation rate in control group was obviously higher than that in observation group (P<0.05). The number of tumor blood vessels in cells in control group was obviously reduced compared with that in observation group (P<0.05). lincRNA-p21 can significantly downregulate the level of HIF-1α, thus downregulating the expression of VEGF and affecting the cell proliferation, apoptosis and migration.

References

1 

Zhou Y, Ren H, Dai B, Li J, Shang L, Huang J and Shi X: Hepatocellular carcinoma-derived exosomal miRNA-21 contributes to tumor progression by converting hepatocyte stellate cells to cancer-associated fibroblasts. J Exp Clin Cancer Res. 37:3242018. View Article : Google Scholar : PubMed/NCBI

2 

Liao ZB, Tan XL, Dong KS, Zhang HW, Chen XP, Chu L and Zhang BX: miRNA-448 inhibits cell growth by targeting BCL-2 in hepatocellular carcinoma. Dig Liver Dis. Sep 28–2018.(Epub ahead of print). View Article : Google Scholar

3 

Pei Y, Sun X, Guo X, Yin H, Wang L, Tian F, Jing H, Liang X, Xu J and Shi P: FGF8 promotes cell proliferation and resistance to EGFR inhibitors via upregulation of EGFR in human hepatocellular carcinoma cells. Oncol Rep. 38:2205–2210. 2017. View Article : Google Scholar : PubMed/NCBI

4 

Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, Khalil AM, Zuk O, Amit I, Rabani M, et al: A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 142:409–419. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Talkowski ME, Maussion G, Crapper L, Rosenfeld JA, Blumenthal I, Hanscom C, Chiang C, Lindgren A, Pereira S, Ruderfer D, et al: Disruption of a large intergenic noncoding RNA in subjects with neurodevelopmental disabilities. Am J Hum Genet. 91:1128–1134. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Pan Y, Li C, Chen J, Zhang K, Chu X, Wang R and Chen L: The emerging roles of long noncoding RNA ROR (lincRNA-ROR) and its possible mechanisms in human cancers. Cell Physiol Biochem. 40:219–229. 2016. View Article : Google Scholar : PubMed/NCBI

7 

Zhou P and Sun L, Liu D, Liu C and Sun L: Long non-coding RNA lincRNA-ROR promotes the progression of colon cancer and holds prognostic value by associating with miR-145. Pathol Oncol Res. 22:733–740. 2016. View Article : Google Scholar : PubMed/NCBI

8 

Dimitrova N, Zamudio JR, Jong RM, Soukup D, Resnick R, Sarma K, Ward AJ, Raj A, Lee JT, Sharp PA, et al: LincRNA-p21 activates p21 in cis to promote Polycomb target gene expression and to enforce the G1/S checkpoint. Mol Cell. 54:777–790. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Yang N, Fu Y, Zhang H, Sima H, Zhu N and Yang G: LincRNA-p21 activates endoplasmic reticulum stress and inhibits hepatocellular carcinoma. Oncotarget. 6:28151–28163. 2015.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 

Wang G, Li Z, Zhao Q, Zhu Y, Zhao C, Li X, Ma Z, Li X and Zhang Y: LincRNA-p21 enhances the sensitivity of radiotherapy for human colorectal cancer by targeting the Wnt/β-catenin signaling pathway. Oncol Rep. 31:1839–1845. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Jiang YJ and Bikle DD: LncRNA profiling reveals new mechanism for VDR protection against skin cancer formation. J Steroid Biochem Mol Biol. 144:87–90. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Işın M, Uysaler E, Özgür E, Köseoğlu H, Şanlı Ö, Yücel ÖB, Gezer U and Dalay N: Exosomal lncRNA-p21 levels may help to distinguish prostate cancer from benign disease. Front Genet. 6:1682015.PubMed/NCBI

14 

Zhai H, Fesler A, Schee K, Fodstad O, Flatmark K and Ju J: Clinical significance of long intergenic noncoding RNA-p21 in colorectal cancer. Clin Colorectal Cancer. 12:261–266. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Castellano JJ, Navarro A, Viñolas N, Marrades RM, Moises J, Cordeiro A, Saco A, Muñoz C, Fuster D, Molins L, et al: LincRNA-p21 impacts prognosis in resected non-small cell lung cancer patients through angiogenesis regulation. J Thorac Oncol. 11:2173–2182. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Jia M, Jiang L, Wang YD, Huang JZ, Yu M and Xue HZ: lincRNA-p21 inhibits invasion and metastasis of hepatocellular carcinoma through Notch signaling-induced epithelial-mesenchymal transition. Hepatol Res. 46:1137–1144. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Schofield CJ and Ratcliffe PJ: Oxygen sensing by HIF hydroxylases. Nat Rev Mol Cell Biol. 5:343–354. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Bartrons R and Caro J: Hypoxia, glucose metabolism and the Warburg's effect. J Bioenerg Biomembr. 39:223–229. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Yu J, Liang F, Huang H, Pirttiniemi P and Yu D: Effects of loading on chondrocyte hypoxia, HIF-1α and VEGF in the mandibular condylar cartilage of young rats. Orthod Craniofac Res. 21:41–47. 2018. View Article : Google Scholar : PubMed/NCBI

20 

Dewangan J, Kaushik S, Rath SK and Balapure AK: Centchroman regulates breast cancer angiogenesis via inhibition of HIF-1α/VEGFR2 signalling axis. Life Sci. 193:9–19. 2018. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

June 2019
Volume 17 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Ye, Y., Peng, Y., Li, Y., Liu, C., Xu, Y., & Li, W. (2019). Effect of lincRNA-p21 targeting HIF-1α on biological functions of liver cancer cells . Oncology Letters, 17, 4964-4968. https://doi.org/10.3892/ol.2019.10195
MLA
Ye, Y., Peng, Y., Li, Y., Liu, C., Xu, Y., Li, W."Effect of lincRNA-p21 targeting HIF-1α on biological functions of liver cancer cells ". Oncology Letters 17.6 (2019): 4964-4968.
Chicago
Ye, Y., Peng, Y., Li, Y., Liu, C., Xu, Y., Li, W."Effect of lincRNA-p21 targeting HIF-1α on biological functions of liver cancer cells ". Oncology Letters 17, no. 6 (2019): 4964-4968. https://doi.org/10.3892/ol.2019.10195