Linc‑pint overexpression inhibits the growth of gastric tumors by downregulating HIF‑1α

Hong,Lei; Wang,Junyan; Wang,Haijuan; Wei,Suju; Zhang,Fan; Han,Jing; Liu,Yan; Ma,Minting; Liu,Chengyuan; Xu,Yu; Liu,Wei

doi:10.3892/mmr.2019.10531

Linc‑pint overexpression inhibits the growth of gastric tumors by downregulating HIF‑1α

Authors:
- Lei Hong
- Junyan Wang
- Haijuan Wang
- Suju Wei
- Fan Zhang
- Jing Han
- Yan Liu
- Minting Ma
- Chengyuan Liu
- Yu Xu
- Wei Liu
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Affiliations: Department of Medical Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050019, P.R. China, Examination and Training Center, Health and Family Planning Commission of Hebei, Shijiazhuang, Hebei 050051, P.R. China
Published online on: July 25, 2019 https://doi.org/10.3892/mmr.2019.10531
Pages: 2875-2881

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Abstract

Long intergenic non‑protein coding RNA, p53 induced transcript (Linc‑pint) has been reported to be downregulated in various cancer cell lines; however, its expression profile and role in gastric cancer remains unknown. The present study aimed to investigate the involvement of Linc‑pint in gastric cancer. Through quantitative polymerase chain reaction, western blotting and viability assays, it was observed that Linc‑pint expression was significantly downregulated in gastric biopsies from patients with gastric cancer, compared with healthy controls. Conversely, the expression of hypoxia‑inducible factor‑1α (HIF‑1α) mRNA was significantly upregulated in patients with gastric cancer compared with in healthy controls. Using a variety of statistical inference tests, including receiver operating characteristic curve and correlation analyses, it was determined that the expression levels of Linc‑pint and HIF‑1α exhibited a significantly negative correlation in patients with gastric cancer but not in healthy controls. Linc‑pint expression was significantly and inversely associated with tumor size but not tumor metastasis. Linc‑pint overexpression inhibited the proliferation of gastric cancer cells, whereas treatment with exogenous HIF‑1α promoted proliferation. Linc‑pint overexpression downregulated the expression of HIF‑1α, whereas exogenous HIF‑1α did not significantly alter Linc‑pint expression. Furthermore, treatment with exogenous HIF‑1α suppressed the inhibitory effects of Linc‑pint overexpression on the proliferation of gastric cancer cells. In conclusion, overexpression of Linc‑pint may inhibit the growth of gastric tumors via downregulation of HIF‑1α.

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1	Warburg O: On the origin of cancer cells. Science. 123:309–314. 1956. View Article : Google Scholar : PubMed/NCBI
2	Rattan R, Giri S, Hartmann LC and Shridhar V: Metformin attenuates ovarian cancer cell growth in an AMP-kinase dispensable manner. J Cell Mol Med. 15:166–178. 2011. View Article : Google Scholar : PubMed/NCBI
3	Karimi P, Islami F, Anandasabapathy S, Freedman ND and Kamangar F: Gastric cancer: Descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev. 23:700–713. 2014. View Article : Google Scholar : PubMed/NCBI
4	Chen W, Zheng R, Zhang S, Zhao P, Zeng H, Zou X and He J: Annual report on status of cancer in China, 2010. Chin J Cancer Res. 26:48–58. 2014.PubMed/NCBI
5	Xiao X, Hao M, Yang XY, Ba Q, Li M, Ni SJ, Wang LS and Du X: Licochalcone A inhibits growth of gastric cancer cells by arresting cell cycle progression and inducing apoptosis. Cancer Lett. 302:69–75. 2011. View Article : Google Scholar : PubMed/NCBI
6	Kataoka Y, Mukohara T, Tomioka H, Funakoshi Y, Kiyota N, Fujiwara Y, Yashiro M, Hirakawa K, Hirai M and Minami H: Foretinib (GSK1363089), a multi-kinase inhibitor of MET and VEGFRs, inhibits growth of gastric cancer cell lines by blocking inter-receptor tyrosine kinase networks. Invest New Drugs. 30:1352–1360. 2012. View Article : Google Scholar : PubMed/NCBI
7	Masoud GN and Li W: HIF-1α pathway: Role, regulation and intervention for cancer therapy. Acta Pharm Sin. 5:378–389. 2015. View Article : Google Scholar
8	Harris AL: Hypoxia-a key regulatory factor in tumour growth. Nat Rev Cancer. 2:38–45. 2002. View Article : Google Scholar : PubMed/NCBI
9	Stoeltzing O, McCarty MF, Wey JS, Fan F, Liu W, Belcheva A, Bucana CD, Semenza GL and Ellis LM: Role of hypoxia-inducible factor 1 alpha in gastric cancer cell growth, angiogenesis, and vessel maturation. J Natl Cancer Inst. 96:946–956. 2004. View Article : Google Scholar : PubMed/NCBI
10	Li L, Zhang GQ, Chen H, Zhao ZJ, Chen HZ, Liu H, Wang G, Jia YH, Pan SH, Kong R, et al: Plasma and tumor levels of Linc-pint are diagnostic and prognostic biomarkers for pancreatic cancer. Oncotarget. 7:71773–71781. 2016.PubMed/NCBI
11	Marín-Béjar O, Mas AM, González J, Martinez D, Athie A, Morales X, Galduroz M, Raimondi I, Grossi E, Guo S, et al: The human lncRNA LINC-PINT inhibits tumor cell invasion through a highly conserved sequence element. Genome Biol. 118:2022017. View Article : Google Scholar
12	Yang F, Zhang H, Mei Y and Wu M: Reciprocal regulation of HIF-1α and lincRNA-p21 modulates the Warburg effect. Mol Cell. 53:88–100. 2014. View Article : Google Scholar : PubMed/NCBI
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
14	McLean MH and El-Omar EM: Genetics of gastric cancer. Nat Rev Gastroenterol Hepatol. 11:664–674. 2014. View Article : Google Scholar : PubMed/NCBI
15	Wang J, Ni Z, Duan Z, Wang G and Li F: Altered expression of hypoxia-inducible factor-1α (HIF-1α) and its regulatory genes in gastric cancer tissues. PLoS One. 9:e998352014. View Article : Google Scholar : PubMed/NCBI
16	Zhao Q, Li Y, Tan B, Fan LQ, Yang PG and Tian Y: HIF-1α induces multidrug resistance in gastric cancer cells by inducing miR-27a. PLoS One. 10:e01327462015. View Article : Google Scholar : PubMed/NCBI
17	Zhang K, Shi H, Xi H, Wu X, Cui J, Gao Y, Liang W, Hu C, Liu Y, Li J, et al: Genome-wide lncRNA microarray profiling identifies novel circulating lncRNAs for detection of gastric cancer. Theranostics. 7:213–227. 2017. View Article : Google Scholar : PubMed/NCBI
18	Luo F, Liu X, Ling M, Lu L, Shi L, Lu X, Li J, Zhang A and Liu Q: The lncRNA MALAT1, acting through HIF-1α stabilization, enhances arsenite-induced glycolysis in human hepatic L-02 cells. Biochim Biophys Acta. 1862:1685–1695. 2016. View Article : Google Scholar : PubMed/NCBI
19	Zhang L, Luo X, Chen F, Yuan W, Xiao X, Zhang X, Dong Y, Zhang Y and Liu Y: LncRNA SNHG1 regulates cerebrovascular pathologies as a competing endogenous RNA through HIF-1α/VEGF signaling in ischemic stroke. J Cell Biochem. 119:5460–5472. 2018. View Article : Google Scholar : PubMed/NCBI
20	Hong Q, Li O, Zheng W, Xiao WZ, Zhang L, Wu D, Cai GY, He JC and Chen XM: LncRNA HOTAIR regulates HIF-1α/AXL signaling through inhibition of miR-217 in renal cell carcinoma. Cell Death Dis. 8:e27722017. View Article : Google Scholar : PubMed/NCBI
21	Marin-Hernandez A, Gallardo-Perez JC, Ralph SJ, Rodríguez-Enríquez S and Moreno-Sánchez R: HIF-1 alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms. Mini Rev Med Chem. 9:1084–1101. 2009. View Article : Google Scholar : PubMed/NCBI