Long non‑coding RNA SNHG7 inhibits NLRP3‑dependent pyroptosis by targeting the miR‑34a/SIRT1 axis in liver cancer

Chen,Zhaohong; He,Miao; Chen,Junhua; Li,Chao; Zhang,Qianshi

doi:10.3892/ol.2020.11635

Long non‑coding RNA SNHG7 inhibits NLRP3‑dependent pyroptosis by targeting the miR‑34a/SIRT1 axis in liver cancer

Authors:
- Zhaohong Chen
- Miao He
- Junhua Chen
- Chao Li
- Qianshi Zhang
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Affiliations: Department of Oncology, People's Hospital of Deyang City, Deyang, Sichuan 618000, P.R. China
Published online on: May 18, 2020 https://doi.org/10.3892/ol.2020.11635
Pages: 893-901
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long non‑coding RNA small nucleolar RNA host gene 7 (SNHG7) is involved in a variety of different types of cancer; however, the role of SNHG7 during liver cancer progression is not completely understood. The aim of the present study was to investigate the functional role and regulatory mechanism underlying SNHG7 during liver cancer. A total of 25 paired hepatocellular carcinoma (HCC) tumor tissues and adjacent normal tissues were collected. Reverse transcription‑quantitative PCR and western blotting were performed to detect the expression levels of SNHG7, microRNA (miR)‑34a, sirtuin 1 (SIRT1) and pyroptosis‑related targets. RNA fluorescence in situ hybridization was performed to detect the expression of SNHG7 in HCC tissues. SNHG7 expression was upregulated in HCC tissues and liver cancer cells compared with normal tissues and normal liver cell lines. High expression of SNHG7 inhibited NLR family pyrin domain containing 3 (NLRP3)‑dependent pyroptosis in HepG2 and SK‑hep‑1 cells. Bioinformatics analysis and dual‑luciferase reporter assays were performed to investigate the interactions between miR‑34a and SNHG7 or SIRT1. SNHG7 served as a competing endogenous RNA of miR‑34a, and SIRT1 was identified as a direct target of miR‑34a. Cell pyroptosis was evaluated by TUNEL and lactate dehydrogenase release assays. SNHG7 knockdown reduced SIRT1 expression, but increased the expression levels of NLRP3, caspase‑1 and interleukin‑1β, leading to pyroptosis. SNHG7 knockdown‑induced effects were enhanced by miR‑34a upregulation. In summary, the present study indicated that the SNHG7/miR‑34a/SIRT1 axis contributed to NLRP3‑dependent pyroptosis during liver cancer.

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1	Gerbes A, Zoulim F, Tilg H, Dufour JF, Bruix J, Paradis V, Salem R, Peck-Radosavljevic M, Galle PR, Greten TF, et al: Gut roundtable meeting paper: Selected recent advances in hepatocellular carcinoma. Gut. 67:380–388. 2018. View Article : Google Scholar : PubMed/NCBI
2	Dhir M, Melin AA, Douaiher J, Lin C, Zhen WK, Hussain SM, Geschwind JF, Doyle MB, Abou-Alfa GK and Are C: A review and update of treatment options and controversies in the management of hepatocellular carcinoma. Ann Surg. 263:1112–1125. 2016. View Article : Google Scholar : PubMed/NCBI
3	Franchi L, Eigenbrod T, Muñoz-Planillo R and Nuñez G: The inflammasome: A caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol. 10:241–247. 2009. View Article : Google Scholar : PubMed/NCBI
4	Greten FR and Grivennikov SI: Inflammation and cancer: Triggers, mechanisms, and consequences. Immunity. 51:27–41. 2019. View Article : Google Scholar : PubMed/NCBI
5	Kantono M and Guo B: Inflammasomes and cancer: The dynamic role of the inflammasome in tumor development. Front Immunol. 8:11322017. View Article : Google Scholar : PubMed/NCBI
6	He Y, Hara H and Núñez G: Mechanism and regulation of NLRP3 inflammasome activation. Trends Biochem Sci. 41:1012–1021. 2016. View Article : Google Scholar : PubMed/NCBI
7	Strowig T, Henao-Mejia J, Elinav E and Flavell R: Inflammasomes in health and disease. Nature. 481:278–286. 2012. View Article : Google Scholar : PubMed/NCBI
8	Wei Q, Mu K, Li T, Zhang Y, Yang Z, Jia X, Zhao W, Huai W, Guo P and Han L: Deregulation of the NLRP3 inflammasome in hepatic parenchymal cells during liver cancer progression. Lab Invest. 94:52–62. 2014. View Article : Google Scholar : PubMed/NCBI
9	Chu Q, Jiang Y, Zhang W, Xu C, Du W, Tuguzbaeva G, Qin Y, Li A, Zhang L, Sun G, et al: Pyroptosis is involved in the pathogenesis of human hepatocellular carcinoma. Oncotarget. 7:84658–84665. 2016. View Article : Google Scholar : PubMed/NCBI
10	Cheetham SW, Gruhl F, Mattick JS and Dinger ME: Long noncoding RNAs and the genetics of cancer. Br J Cancer. 108:2419–2425. 2013. View Article : Google Scholar : PubMed/NCBI
11	Mattick JS and Makunin IV: Non-coding RNA. Hum Mol Genet. 15:R17–R29. 2006. View Article : Google Scholar : PubMed/NCBI
12	Cui H, Zhang Y, Zhang Q, Chen W, Zhao H and Liang J: A comprehensive genome-wide analysis of long noncoding RNA expression profile in hepatocellular carcinoma. Cancer Med. 6:2932–2941. 2017. View Article : Google Scholar : PubMed/NCBI
13	Yang X, Sun L, Wang L, Yao B, Mo H and Yang W: lncRNA SNHG7 accelerates the proliferation, migration and invasion of hepatocellular carcinoma cells via regulating miR-122-5p and RPL4. Biomed Pharmacother. 118:1093862019. View Article : Google Scholar : PubMed/NCBI
14	Li Y, Zeng C, Hu J, Pan Y, Shan Y, Liu B and Jia L: Long non-coding RNA-SNHG7 acts as a target of miR-34a to increase GALNT7 level and regulate PI3K/Akt/mTOR pathway in colorectal cancer progression. J Hematol Oncol. 11:892018. View Article : Google Scholar : PubMed/NCBI
15	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
16	Yu F, Dong P, Mao Y, Zhao B, Huang Z and Zheng J: Loss of lncRNA-SNHG7 promotes the suppression of hepatic stellate cell activation via miR-378a-3p and DVL2. Mol Ther Nucleic Acids. 17:235–244. 2019. View Article : Google Scholar : PubMed/NCBI
17	Lu S, Xu J, Xu X, Hu S, Li B and Li W: The expression of astrocyte elevated gene-1 in human non-small-cell lung cancer and its relationship with postoperative chemotherapy and radiotherapy. Histopathology. 67:817–826. 2015. View Article : Google Scholar : PubMed/NCBI
18	Huo X, Han S, Wu G, Latchoumanin O, Zhou G, Hebbard L, George J and Qiao L: Dysregulated long noncoding RNAs (lncRNAs) in hepatocellular carcinoma: Implications for tumorigenesis, disease progression, and liver cancer stem cells. Mol Cancer. 16:1652017. View Article : Google Scholar : PubMed/NCBI
19	Li Y, Wang P, Yang X, Wang W, Zhang J, He Y, Zhang W, Jing T, Wang B and Lin R: SIRT1 inhibits inflammatory response partly through regulation of NLRP3 inflammasome in vascular endothelial cells. Mol Immunol. 77:148–156. 2016. View Article : Google Scholar : PubMed/NCBI
20	Rayamajhi M, Zhang Y and Miao EA: Detection of pyroptosis by measuring released lactate dehydrogenase activity. Methods Mol Biol. 1040:85–90. 2013. View Article : Google Scholar : PubMed/NCBI
21	Shan Y, Ma J, Pan Y, Hu J, Liu B and Jia L: lncRNA SNHG7 sponges miR-216b to promote proliferation and liver metastasis of colorectal cancer through upregulating GALNT1. Cell Death Dis. 9:7222018. View Article : Google Scholar : PubMed/NCBI
22	She K, Huang J, Zhou H, Huang T, Chen G and He J: lncRNA-SNHG7 promotes the proliferation, migration and invasion and inhibits apoptosis of lung cancer cells by enhancing the FAIM2 expression. Oncol Rep. 36:2673–2680. 2016. View Article : Google Scholar : PubMed/NCBI
23	Wang MW, Liu J, Liu Q, Xu QH, Li TF, Jin S and Xia TS: LncRNA SNHG7 promotes the proliferation and inhibits apoptosis of gastric cancer cells by repressing the P15 and P16 expression. Eur Rev Med Pharmacol Sci. 21:4613–4622. 2017.PubMed/NCBI
24	Qi H, Wen B, Wu Q, Cheng W, Lou J, Wei J, Huang J, Yao X and Weng G: Long noncoding RNA SNHG7 accelerates prostate cancer proliferation and cycle progression through cyclin D1 by sponging miR-503. Biomed Pharmacother. 102:326–332. 2018. View Article : Google Scholar : PubMed/NCBI
25	Ren J, Yang Y, Xue J, Xi Z, Hu L, Pan SJ and Sun Q: Long noncoding RNA SNHG7 promotes the progression and growth of glioblastoma via inhibition of miR-5095. Biochem Biophys Res Commun. 496:712–718. 2018. View Article : Google Scholar : PubMed/NCBI
26	Sun BZ, Ji DG, Feng ZX and Wang Y: Long noncoding RNA SNHG7 represses the expression of RBM5 to strengthen metastasis of hepatocellular carcinoma. Eur Rev Med Pharmacol Sci. 23:5699–5704. 2019.PubMed/NCBI
27	Li J, Yang C, Li Y, Chen A, Li L and You Z: lncRNA GAS5 suppresses ovarian cancer by inducing inflammasome formation. Biosci Rep. 38(pii): BSR201711502018. View Article : Google Scholar : PubMed/NCBI
28	Zhang HF, Wang YC and Han YD: MicroRNA-34a inhibits liver cancer cell growth by reprogramming glucose metabolism. Mol Med Rep. 17:4483–4489. 2018.PubMed/NCBI
29	Slabáková E, Culig Z, Remšík J and Souček K: Alternative mechanisms of miR-34a regulation in cancer. Cell Death Dis. 8:e31002017. View Article : Google Scholar : PubMed/NCBI
30	Li X and Kazgan N: Mammalian sirtuins and energy metabolism. Int J Biol Sci. 7:575–587. 2011. View Article : Google Scholar : PubMed/NCBI
31	Zheng T, Wang J, Jiang H and Liu L: Hippo signaling in oval cells and hepatocarcinogenesis. Cancer Lett. 302:91–99. 2011. View Article : Google Scholar : PubMed/NCBI
32	Fang Y and Nicholl MB: Sirtuin 1 in malignant transformation: Friend or foe? Cancer Lett. 306:10–14. 2011. View Article : Google Scholar : PubMed/NCBI
33	Portmann S, Fahrner R, Lechleiter A, Keogh A, Overney S, Laemmle A, Mikami K, Montani M, Tschan MP, Candinas D and Stroka D: Antitumor effect of SIRT1 inhibition in human HCC tumor models in vitro and in vivo. Mol Cancer Ther. 12:499–508. 2013. View Article : Google Scholar : PubMed/NCBI