MicroRNA-3666-induced suppression of SIRT7 inhibits the growth of non-small cell lung cancer cells

Shi,Hongyang; Ji,Yuqiang; Zhang,Dexin; Liu,Yun; Fang,Ping

doi:10.3892/or.2016.5063

MicroRNA-3666-induced suppression of SIRT7 inhibits the growth of non-small cell lung cancer cells

Authors:
- Hongyang Shi
- Yuqiang Ji
- Dexin Zhang
- Yun Liu
- Ping Fang
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Affiliations: Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Department of Cardiovascular Disease, Xi'an No.1 Hospital, Xi'an, Shaanxi 710002, P.R. China
Published online on: September 5, 2016 https://doi.org/10.3892/or.2016.5063
Pages: 3051-3057

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Abstract

Sirtuin7 (SIRT7) plays an important role in many cancer types, but its function in non-small cell lung cancer (NSCLC) remains unclear. This study investigated the biological role and underlying mechanism of SIRT7 in NSCLC. Results showed that SIRT7 was highly expressed in NSCLC cell lines, as detected by real-time quantitative polymerase chain reaction and western blot analysis. SIRT7 knockdown by small interfering RNA (siRNA) significantly inhibited the growth of NSCLC cells and induced their apoptosis. Bioinformatics algorithms indicated that SIRT7 was a putative target of microRNA-3666 (miR-3666). Dual-luciferase reporter assay demonstrated that miR-3666 could target the 3'-untranslated region of SIRT7. Western blot analysis revealed that miR-3666 could regulate the protein expression of SIRT7. The miR-3666 overexpression significantly inhibited NSCLC cell growth. The restoration of SIRT7 protein expression significantly abrogated the effect of the miR-3666 overexpression. Moreover, SIRT7 depletion induced by siRNA or miR-3666 overexpression promoted the expression of pro-apoptotic genes. Taken together, our study suggests that SIRT7 functions as an oncogene in NSCLC, and miR-3666 can target SIRT7 to inhibit NSCLC cell growth by promoting the pro-apoptotic signaling pathway. Thus, this study provides novel insights into the development of new and potential treatments for NSCLC.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
2	Qiu ZX, Sun RF, Mo XM and Li WM: The p70S6K specific inhibitor PF-4708671 impedes non-small cell lung cancer growth. PLoS One. 11:e01471852016. View Article : Google Scholar : PubMed/NCBI
3	Zhang C, Zhang H, Shi J, Wang D, Zhang X, Yang J, Zhai Q and Ma A: Trial-based cost-utility analysis of icotinib versus gefitinib as second-line therapy for advanced non-small cell lung cancer in China. PLoS One. 11:e01518462016. View Article : Google Scholar : PubMed/NCBI
4	Steeg PS: Metastasis suppressors alter the signal transduction of cancer cells. Nat Rev Cancer. 3:55–63. 2003. View Article : Google Scholar : PubMed/NCBI
5	Houtkooper RH, Pirinen E and Auwerx J: Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol. 13:225–238. 2012.PubMed/NCBI
6	Bosch-Presegué L and Vaquero A: The dual role of sirtuins in cancer. Genes Cancer. 2:648–662. 2011. View Article : Google Scholar : PubMed/NCBI
7	North BJ and Verdin E: Sirtuins: Sir2-related NAD-dependent protein deacetylases. Genome Biol. 5:2242004. View Article : Google Scholar : PubMed/NCBI
8	Matsushima S and Sadoshima J: The role of sirtuins in cardiac disease. Am J Physiol Heart Circ Physiol. 309:H1375–H1389. 2015. View Article : Google Scholar : PubMed/NCBI
9	Michishita E, Park JY, Burneskis JM, Barrett JC and Horikawa I: Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell. 16:4623–4635. 2005. View Article : Google Scholar : PubMed/NCBI
10	Meng X, Tan J, Li M, Song S, Miao Y and Zhang Q: Sirt1: Role under the condition of ischemia/hypoxia. Cell Mol Neurobiol. Mar 14–2016.Epub ahead of print. View Article : Google Scholar
11	Donmez G and Outeiro TF: SIRT1 and SIRT2: Emerging targets in neurodegeneration. EMBO Mol Med. 5:344–352. 2013. View Article : Google Scholar : PubMed/NCBI
12	Lombard DB, Alt FW, Cheng HL, Bunkenborg J, Streeper RS, Mostoslavsky R, Kim J, Yancopoulos G, Valenzuela D, Murphy A, et al: Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol. 27:8807–8814. 2007. View Article : Google Scholar : PubMed/NCBI
13	Onyango P, Celic I, McCaffery JM, Boeke JD and Feinberg AP: SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria. Proc Natl Acad Sci USA. 99:13653–13658. 2002. View Article : Google Scholar : PubMed/NCBI
14	Nakagawa T, Lomb DJ, Haigis MC and Guarente L: SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell. 137:560–570. 2009. View Article : Google Scholar : PubMed/NCBI
15	Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ, Valenzuela DM, Yancopoulos GD, Karow M, Blander G, et al: SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell. 126:941–954. 2006. View Article : Google Scholar : PubMed/NCBI
16	Mao Z, Hine C, Tian X, Van Meter M, Au M, Vaidya A, Seluanov A and Gorbunova V: SIRT6 promotes DNA repair under stress by activating PARP1. Science. 332:1443–1446. 2011. View Article : Google Scholar : PubMed/NCBI
17	McCord RA, Michishita E, Hong T, Berber E, Boxer LD, Kusumoto R, Guan S, Shi X, Gozani O, Burlingame AL, et al: SIRT6 stabilizes DNA-dependent protein kinase at chromatin for DNA double-strand break repair. Aging (Albany, NY). 1:109–121. 2009. View Article : Google Scholar
18	Kiran S, Anwar T, Kiran M and Ramakrishna G: Sirtuin 7 in cell proliferation, stress and disease: Rise of the seventh sirtuin! Cell Signal. 27:673–682. 2015. View Article : Google Scholar
19	Ford E, Voit R, Liszt G, Magin C, Grummt I and Guarente L: Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription. Genes Dev. 20:1075–1080. 2006. View Article : Google Scholar : PubMed/NCBI
20	Grob A, Roussel P, Wright JE, McStay B, Hernandez-Verdun D and Sirri V: Involvement of SIRT7 in resumption of rDNA transcription at the exit from mitosis. J Cell Sci. 122:489–498. 2009. View Article : Google Scholar : PubMed/NCBI
21	Kim JK, Noh JH, Jung KH, Eun JW, Bae HJ, Kim MG, Chang YG, Shen Q, Park WS, Lee JY, et al: Sirtuin7 oncogenic potential in human hepatocellular carcinoma and its regulation by the tumor suppressors MiR-125a-5p and MiR-125b. Hepatology. 57:1055–1067. 2013. View Article : Google Scholar
22	Yu H, Ye W, Wu J, Meng X, Liu RY, Ying X, Zhou Y, Wang H, Pan C and Huang W: Overexpression of sirt7 exhibits oncogenic property and serves as a prognostic factor in colorectal cancer. Clin Cancer Res. 20:3434–3445. 2014. View Article : Google Scholar : PubMed/NCBI
23	Ebrahimi A and Sadroddiny E: MicroRNAs in lung diseases: Recent findings and their pathophysiological implications. Pulm Pharmacol Ther. 34:55–63. 2015. View Article : Google Scholar : PubMed/NCBI
24	Mendell JT and Olson EN: MicroRNAs in stress signaling and human disease. Cell. 148:1172–1187. 2012. View Article : Google Scholar : PubMed/NCBI
25	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
26	Winter J, Jung S, Keller S, Gregory RI and Diederichs S: Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol. 11:228–234. 2009. View Article : Google Scholar : PubMed/NCBI
27	Cortinovis D, Monica V, Pietrantonio F, Ceresoli GL, La Spina CM and Wannesson L: MicroRNAs in non-small cell lung cancer: Current status and future therapeutic promises. Curr Pharm Des. 20:3982–3990. 2014. View Article : Google Scholar
28	Feng B, Zhang K, Wang R and Chen L: Non-small-cell lung cancer and miRNAs: Novel biomarkers and promising tools for treatment. Clin Sci (Lond). 128:619–634. 2015. View Article : Google Scholar
29	Barger JF and Nana-Sinkam SP: MicroRNA as tools and therapeutics in lung cancer. Respir Med. 109:803–812. 2015. View Article : Google Scholar : PubMed/NCBI
30	Li L, Han LY, Yu M, Zhou Q, Xu JC and Li P: Pituitary tumor-transforming gene 1 enhances metastases of cervical cancer cells through miR-3666-regulated ZEB1. Tumour Biol. 2015:Sep 17–2015.Epub ahead of print.
31	Wang G, Cai C and Chen L: MicroRNA-3666 regulates thyroid carcinoma cell proliferation via MET. Cell Physiol Biochem. 38:1030–1039. 2016. View Article : Google Scholar : PubMed/NCBI
32	Barber MF, Michishita-Kioi E, Xi Y, Tasselli L, Kioi M, Moqtaderi Z, Tennen RI, Paredes S, Young NL, Chen K, et al: SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation. Nature. 487:114–118. 2012.PubMed/NCBI
33	Singh S, Kumar PU, Thakur S, Kiran S, Sen B, Sharma S, Rao VV, Poongothai AR and Ramakrishna G: Expression/localization patterns of sirtuins (SIRT1, SIRT2, and SIRT7) during progression of cervical cancer and effects of sirtuin inhibitors on growth of cervical cancer cells. Tumour Biol. 36:6159–6171. 2015. View Article : Google Scholar : PubMed/NCBI
34	Zhang S, Chen P, Huang Z, Hu X, Chen M, Hu S, Hu Y and Cai T: Sirt7 promotes gastric cancer growth and inhibits apoptosis by epigenetically inhibiting miR-34a. Sci Rep. 5:97872015. View Article : Google Scholar : PubMed/NCBI
35	Wang HL, Lu RQ, Xie SH, Zheng H, Wen XM, Gao X and Guo L: SIRT7 exhibits oncogenic potential in human ovarian cancer cells. Asian Pac J Cancer Prev. 16:3573–3577. 2015. View Article : Google Scholar : PubMed/NCBI
36	Aljada A, Saleh AM, Alkathiri M, Shamsa HB, Al-Bawab A and Nasr A: Altered sirtuin 7 expression is associated with early stage breast cancer. Breast Cancer (Auckl). 9:3–8. 2015.
37	Geng Q, Peng H, Chen F, Luo R and Li R: High expression of Sirt7 served as a predictor of adverse outcome in breast cancer. Int J Clin Exp Pathol. 8:1938–1945. 2015.PubMed/NCBI
38	McGlynn LM, McCluney S, Jamieson NB, Thomson J, MacDonald AI, Oien K, Dickson EJ, Carter CR, McKay CJ and Shiels PG: SIRT3 & SIRT7: Potential novel biomarkers for determining outcome in pancreatic cancer patients. PLoS One. 10:e01313442015. View Article : Google Scholar :
39	Aljada A, Saleh AM and Al Suwaidan S: Modulation of insulin/IGFs pathways by sirtuin-7 inhibition in drug-induced chemoreistance. Diagn Pathol. 9:942014. View Article : Google Scholar : PubMed/NCBI
40	Zhao L and Wang W: miR-125b suppresses the proliferation of hepatocellular carcinoma cells by targeting Sirtuin7. Int J Clin Exp Med. 8:18469–18475. 2015.
41	Han Y, Liu Y, Zhang H, Wang T, Diao R, Jiang Z, Gui Y and Cai Z: Hsa-miR-125b suppresses bladder cancer development by down-regulating oncogene SIRT7 and oncogenic long non-coding RNA MALAT1. FEBS Lett. 587:3875–3882. 2013. View Article : Google Scholar
42	Cioffi M, Vallespinos-Serrano M, Trabulo SM, Fernandez-Marcos PJ, Firment AN, Vazquez BN, Vieira CR, Mulero F, Camara JA, Cronin UP, et al: MiR-93 controls adiposity via inhibition of Sirt7 and Tbx3. Cell Rep. 12:1594–1605. 2015. View Article : Google Scholar : PubMed/NCBI
43	Vakhrusheva O, Smolka C, Gajawada P, Kostin S, Boettger T, Kubin T, Braun T and Bober E: Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice. Circ Res. 102:703–710. 2008. View Article : Google Scholar : PubMed/NCBI
44	Kiran S, Oddi V and Ramakrishna G: Sirtuin 7 promotes cellular survival following genomic stress by attenuation of DNA damage, SAPK activation and p53 response. Exp Cell Res. 331:123–141. 2015. View Article : Google Scholar