miR‑145 inhibits human non‑small-cell lung cancer growth by dual-targeting RIOK2 and NOB1

Liu,Kun; Chen,Honglin; You,Qingsheng; Ye,Qing; Wang,Fei; Wang,Shuo; Zhang,Shuanglong; Yu,Kangjun; Li,Weinan; Gu,Mingming

doi:10.3892/ijo.2018.4393

miR‑145 inhibits human non‑small-cell lung cancer growth by dual-targeting RIOK2 and NOB1

Authors:
- Kun Liu
- Honglin Chen
- Qingsheng You
- Qing Ye
- Fei Wang
- Shuo Wang
- Shuanglong Zhang
- Kangjun Yu
- Weinan Li
- Mingming Gu
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Affiliations: Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, School of Nursing, Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
Published online on: May 3, 2018 https://doi.org/10.3892/ijo.2018.4393
Pages: 257-265

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Abstract

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-associated mortality worldwide. Right open reading frame kinase 2 (RIOK2) and nin one binding protein (NOB1) are important accessory factors in ribosome assembly. In our previous study, RIOK2 and NOB1 were revealed to be highly expressed in NSCLC, and were associated with the clinicopathological characteristics of patients with NSCLC, i.e. TNM clinical stage, lymph node metastasis and differentiation. In addition, RIOK2 expression was correlated with NOB1. To further explore the mechanism and the RIOK2 and NOB1 signaling pathway, microRNA (miR) regulation was analyzed. The tumor suppressor miR‑145 has been reported to be lowly expressed in numerous types of human cancer; in the present study, the expression levels of miR‑145 were decreased in patients with NSCLC. Furthermore, RIOK2 and NOB1 were predicted to be the direct targets of miR‑145 using bioinformatics software; this was further validated using a dual luciferase reporter assay. In addition, the protein expression levels of RIOK2 and NOB1 were inhibited in response to miR‑145 overexpression, thus resulting in the suppression of cell viability, migration and invasion. These results suggested that RIOK2 and NOB1 may be potential targets in the treatment of NSCLC, and miR‑145 may be considered a therapeutic inhibitor of both genes.

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1	Molina JR, Yang P, Cassivi SD, Schild SE and Adjei AA: Non-small cell lung cancer: Epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 83:584–594. 2008. View Article : Google Scholar : PubMed/NCBI
2	Lamanna AC and Karbstein K: Nob1 binds the single-stranded cleavage site D at the 3′-end of 18S rRNA with its PIN domain. Proc Natl Acad Sci USA. 106:14259–14264. 2009. View Article : Google Scholar
3	Liu K, Chen HL, Gu MM and You QS: Relationship between NOB1 expression and prognosis of resected non-small cell lung cancer. Int J Biol Markers. 30:e43–e48. 2015. View Article : Google Scholar
4	Liu K, Gu MM, Chen HL and You QS: NOB1 in non-small-cell lung cancer: Expression profile and clinical significance. Pathol Oncol Res. 20:461–466. 2014. View Article : Google Scholar
5	Kiburu IN and LaRonde-LeBlanc N: Interaction of Rio1 kinase with toyocamycin reveals a conformational switch that controls oligomeric state and catalytic activity. PLoS One. 7:e373712012. View Article : Google Scholar : PubMed/NCBI
6	Darnell JC; Molecular biology: Ribosome rescue and neurodegeneration. Science. 345:378–379. 2014. View Article : Google Scholar : PubMed/NCBI
7	Turowski TW, Lebaron S, Zhang E, Peil L, Dudnakova T, Petfalski E, Granneman S, Rappsilber J and Tollervey D: Rio1 mediates ATP-dependent final maturation of 40S ribosomal subunits. Nucleic Acids Res. 42:12189–12199. 2014. View Article : Google Scholar : PubMed/NCBI
8	Liu K, Chen HL, Wang S, Gu MM, Chen XM, Zhang SL, Yu KJ and You QS: High Expression of RIOK2 and NOB1 Predict human non-small cell lung cancer outcomes. Sci Rep. 6:286662016. View Article : Google Scholar :
9	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar
10	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar
11	Shenouda SK and Alahari SK: MicroRNA function in cancer: Oncogene or a tumor suppressor? Cancer Metastasis Rev. 28:369–378. 2009. View Article : Google Scholar : PubMed/NCBI
12	Gao Y, Zhang Z, Li K, Gong L, Yang Q, Huang X, Hong C, Ding M and Yang H: Linc-DYNC2H1-4 promotes EMT and CSC phenotypes by acting as a sponge of miR-145 in pancreatic cancer cells. Cell Death Dis. 8:e29242017. View Article : Google Scholar : PubMed/NCBI
13	Goto Y, Kurozumi A, Arai T, Nohata N, Kojima S, Okato A, Kato M, Yamazaki K, Ishida Y, Naya Y, et al: Impact of novel miR-145-3p regulatory networks on survival in patients with castration-resistant prostate cancer. Br J Cancer. 117:409–420. 2017. View Article : Google Scholar : PubMed/NCBI
14	Wei H, Wen-Ming C and Jun-Bo J: Plasma miR-145 as a novel biomarker for the diagnosis and radiosensitivity prediction of human cervical cancer. J Int Med Res. 45:1054–1060. 2017. View Article : Google Scholar :
15	Hu CE, Du PZ, Zhang HD and Huang GJ: Long noncoding RNA CRNDE promotes proliferation of gastric cancer cells by targeting miR-145. Cell Physiol Biochem. 42:13–21. 2017. View Article : Google Scholar : PubMed/NCBI
16	Moon S, Kim DK and Kim J: Apoptosis-related microRNA-145-5p enhances the effects of pheophorbide a-based photodynamic therapy in oral cancer. Oncotarget. 8:35184–35192. 2017. View Article : Google Scholar :
17	Sheng N, Tan G, You W, Chen H, Gong J, Chen D, Zhang H and Wang Z: miR-145 inhibits human colorectal cancer cell migration and invasion via PAK4-dependent pathway. Cancer Med. 6:1331–1340. 2017. View Article : Google Scholar :
18	Ding Y, Zhang C, Zhang J, Zhang N, Li T, Fang J, Zhang Y, Zuo F, Tao Z, Tang S, et al: miR-145 inhibits proliferation and migration of breast cancer cells by directly or indirectly regulating TGF-β1 expression. Int J Oncol. 50:1701–1710. 2017. View Article : Google Scholar : PubMed/NCBI
19	Minami K, Taniguchi K, Sugito N, Kuranaga Y, Inamoto T, Takahara K, Takai T, Yoshikawa Y, Kiyama S, Akao Y, et al: miR-145 negatively regulates Warburg effect by silencing KLF4 and PTBP1 in bladder cancer cells. Oncotarget. 8:33064–33077. 2017. View Article : Google Scholar : PubMed/NCBI
20	Liu S, Gao G, Yan D, Chen X, Yao X, Guo S, Li G and Zhao Y: Effects of miR-145-5p through NRAS on the cell proliferation, apoptosis, migration, and invasion in melanoma by inhibiting MAPK and PI3K/AKT pathways. Cancer Med. 6:819–833. 2017. View Article : Google Scholar : PubMed/NCBI
21	Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, Barbisin M, Xu NL, Mahuvakar VR, Andersen MR, et al: Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 33:e1792005. View Article : Google Scholar : PubMed/NCBI
22	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
23	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
24	Ansari J, Shackelford RE and El-Osta H: Epigenetics in non-small cell lung cancer: From basics to therapeutics. Transl Lung Cancer Res. 5:155–171. 2016. View Article : Google Scholar : PubMed/NCBI
25	Reid G, Kao SC, Pavlakis N, Brahmbhatt H, MacDiarmid J, Clarke S, Boyer M and van Zandwijk N: Clinical development of TargomiRs, a miRNA mimic-based treatment for patients with recurrent thoracic cancer. Epigenomics. 8:1079–1085. 2016. View Article : Google Scholar : PubMed/NCBI
26	Zhang Y, Ni J, Zhou G, Yuan J, Ren W, Shan Y, Tang W, Yu L and Zhao S: Cloning, expression and characterization of the human NOB1 gene. Mol Biol Rep. 32:185–189. 2005. View Article : Google Scholar : PubMed/NCBI
27	Lin Y, Peng S, Yu H, Teng H and Cui M: RNAi-mediated downregulation of NOB1 suppresses the growth and colony-formation ability of human ovarian cancer cells. Med Oncol. 29:311–317. 2012. View Article : Google Scholar
28	Lu Z, Guo Q, Shi A, Xie F and Lu Q: Downregulation of NIN/RPN12 binding protein inhibit the growth of human hepatocellular carcinoma cells. Mol Biol Rep. 39:501–507. 2012. View Article : Google Scholar
29	Li XY, Luo QF, Li J, Wei CK, Kong XJ, Zhang JF and Fang L: Clinical significance of NOB1 expression in breast infiltrating ductal carcinoma. Int J Clin Exp Pathol. 6:2137–2144. 2013.PubMed/NCBI
30	Wang H, Li P and Zhao B: Knockdown of NOB1 expression by RNAi inhibits cellular proliferation and migration in human gliomas. Gene. 528:146–153. 2013. View Article : Google Scholar : PubMed/NCBI
31	Lin S, Meng W, Zhang W, Liu J, Wang P, Xue S and Chen G: Expression of the NOB1 gene and its clinical significance in papillary thyroid carcinoma. J Int Med Res. 41:568–572. 2013. View Article : Google Scholar : PubMed/NCBI
32	Liu G, Shen D, Jiao L and Sun Y: Nin one binding protein expression as a prognostic marker in prostate carcinoma. Clin Transl Oncol. 16:843–847. 2014. View Article : Google Scholar : PubMed/NCBI
33	Weinberg F, Reischmann N, Fauth L, Taromi S, Mastroianni J, Köhler M, Halbach S, Becker AC, Deng N, Schmitz T, et al: The atypical kinase RIOK1 promotes tumor growth and invasive behavior. EBioMedicine. 20:79–97. 2017. View Article : Google Scholar : PubMed/NCBI
34	Dolly SO, Collins DC, Sundar R, Popat S and Yap TA: Advances in the development of molecularly targeted agents in non-Small-cell lung cancer. Drugs. 77:813–827. 2017. View Article : Google Scholar : PubMed/NCBI
35	Meerson A, Traurig M, Ossowski V, Fleming JM, Mullins M and Baier LJ: Human adipose microRNA-221 is upregulated in obesity and affects fat metabolism downstream of leptin and TNF-α. Diabetologia. 56:1971–1979. 2013. View Article : Google Scholar : PubMed/NCBI
36	Pertschy B, Schneider C, Gnädig M, Schäfer T, Tollervey D and Hurt E: RNA helicase Prp43 and its co-factor Pfa1 promote 20 to 18 S rRNA processing catalyzed by the endonuclease Nob1. J Biol Chem. 284:35079–35091. 2009. View Article : Google Scholar : PubMed/NCBI
37	Ferreira-Cerca S, Sagar V, Schäfer T, Diop M, Wesseling AM, Lu H, Chai E, Hurt E and LaRonde-LeBlanc N: ATPase-dependent role of the atypical kinase Rio2 on the evolving pre-40S ribosomal subunit. Nat Struct Mol Biol. 19:1316–1323. 2012. View Article : Google Scholar : PubMed/NCBI
38	Woolls HA, Lamanna AC and Karbstein K: Roles of Dim2 in ribosome assembly. J Biol Chem. 286:2578–2586. 2011. View Article : Google Scholar :
39	Campbell MG and Karbstein K: Protein-protein interactions within late pre-40S ribosomes. PLoS One. 6:e161942011. View Article : Google Scholar : PubMed/NCBI