Upregulation of miR-21 expression is a valuable predicator of advanced clinicopathological features and poor prognosis in patients with renal cell carcinoma through the p53/p21‑cyclin E2‑Bax/caspase-3 signaling pathway

Liu,Zhihong; Lu,You; Xiao,Yingmin; Lu,Yipin

doi:10.3892/or.2017.5402

Upregulation of miR-21 expression is a valuable predicator of advanced clinicopathological features and poor prognosis in patients with renal cell carcinoma through the p53/p21‑cyclin E2‑Bax/caspase-3 signaling pathway

Authors:
- Zhihong Liu
- You Lu
- Yingmin Xiao
- Yipin Lu
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Affiliations: Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China, Department of Pediatrics, West China Second University Hospital, Chengdu, Sichuan, P.R. China, Department of Urology of Sichuan Tumor Hospital, Chengdu, Sichuan, P.R. China
Published online on: January 24, 2017 https://doi.org/10.3892/or.2017.5402
Pages: 1437-1444

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Abstract

In the present study, we investigated whether the upregulation of miR-21 expression is a predictor of advanced clinicopathological features and poor prognosis in patients with renal cell carcinoma (RCC). It was found that the expression of miR-21 not only had a significant effect on the clinicopathological features and survival in patients with RCC, but also exerted an important influence on the occurrence rate of RCC. In addition, miR-21 expression was lower in the human kidney HRPTEpiC cell line than that noted in RCC A-498 cells. Meanwhile, the overexpression of miR-21 not only increased cell proliferation, inhibited apoptosis and reduced caspase-3 activity in the A-498 cells, but also suppressed p53, CDKN1A p21, cyclin E2 and Bax protein expression in the A-498 cells. In contrary, the downregulation of miR-21 expression promoted the protein expression of p53, CDKN1A p21 and cyclin E2, and decreased Bax protein expression and caspase-3 activity in the A-498 cells. Our data indicate a clear correlation between miR-21 expression and clinicopathological features and poor prognosis in patients with RCC through the p53/p21-cyclin E2-Bax/caspase-3 signaling pathway.

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1	Ghosh A, Jana M, Modi K, Gonzalez FJ, Sims KB, Berry-Kravis E and Pahan K: Activation of peroxisome proliferator-activated receptor α induces lysosomal biogenesis in brain cells: Implications for lysosomal storage disorders. J Biol Chem. 290:10309–10324. 2015. View Article : Google Scholar : PubMed/NCBI
2	Patterson CM, Wong JM, Leinninger GM, Allison MB, Mabrouk OS, Kasper CL, Gonzalez IE, Mackenzie A, Jones JC, Kennedy RT, et al: Ventral tegmental area neurotensin signaling links the lateral hypothalamus to locomotor activity and striatal dopamine efflux in male mice. Endocrinology. 156:1692–1700. 2015. View Article : Google Scholar : PubMed/NCBI
3	Levy O, Mortensen LJ, Boquet G, Tong Z, Perrault C, Benhamou B, Zhang J, Stratton T, Han E, Safaee H, et al: A small-molecule screen for enhanced homing of systemically infused cells. Cell Reports. 10:1261–1268. 2015. View Article : Google Scholar : PubMed/NCBI
4	Marcu R, Kotha S, Zhi Z, Qin W, Neeley CK, Wang RK, Zheng Y and Hawkins BJ: The mitochondrial permeability transition pore regulates endothelial bioenergetics and angiogenesis. Circ Res. 116:1336–1345. 2015. View Article : Google Scholar : PubMed/NCBI
5	Kannan K, Coarfa C, Chao PW, Luo L, Wang Y, Brinegar AE, Hawkins SM, Milosavljevic A, Matzuk MM and Yen L: Recurrent BCAM-AKT2 fusion gene leads to a constitutively activated AKT2 fusion kinase in high-grade serous ovarian carcinoma. Proc Natl Acad Sci USA. 112:E1272–E1277. 2015. View Article : Google Scholar : PubMed/NCBI
6	Pan MH, Chang YH, Tsai ML, Lai CS, Ho SY, Badmaev V and Ho CT: Pterostilbene suppressed lipopolysaccharide-induced up-expression of iNOS and COX-2 in murine macrophages. J Agric Food Chem. 56:7502–7509. 2008. View Article : Google Scholar : PubMed/NCBI
7	Sayer RD, Wright AJ, Chen N and Campbell WW: Dietary approaches to stop hypertension diet retains effectiveness to reduce blood pressure when lean pork is substituted for chicken and fish as the predominant source of protein. Am J Clin Nutr. 102:302–308. 2015. View Article : Google Scholar : PubMed/NCBI
8	Tsai ML, Lai CS, Chang YH, Chen WJ, Ho CT and Pan MH: Pterostilbene, a natural analogue of resveratrol, potently inhibits 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin carcinogenesis. Food Funct. 3:1185–1194. 2012. View Article : Google Scholar : PubMed/NCBI
9	Li L, Liu S, Xu Y, Zhang A, Jiang J, Tan W, Xing J, Feng G, Liu H, Huo F, et al: Human umbilical cord-derived mesenchymal stem cells downregulate inflammatory responses by shifting the Treg/Th17 profile in experimental colitis. Pharmacology. 92:257–264. 2013. View Article : Google Scholar : PubMed/NCBI
10	Liu W, Konermann A, Guo T, Jäger A, Zhang L and Jin Y: Canonical Wnt signaling differently modulates osteogenic differentiation of mesenchymal stem cells derived from bone marrow and from periodontal ligament under inflammatory conditions. Biochim Biophys Acta. 1840:1125–1134. 2014. View Article : Google Scholar : PubMed/NCBI
11	Aggarwal BB, Gupta SC and Sung B: Curcumin: An orally bioavailable blocker of TNF and other pro-inflammatory biomarkers. Br J Pharmacol. 169:1672–1692. 2013. View Article : Google Scholar : PubMed/NCBI
12	Moore JN, Cook JA, Morris DD, Halushka PV and Wise WC: Endotoxin-induced procoagulant activity, eicosanoid synthesis, and tumor necrosis factor production by rat peritoneal macrophages: Effect of endotoxin tolerance and glucan. Circ Shock. 31:281–295. 1990.PubMed/NCBI
13	Park K, Ju WC, Yeo JH, Kim JY, Seo HS, Uchida Y and Cho Y: Increased OPG/RANKL ratio in the conditioned medium of soybean-treated osteoblasts suppresses RANKL-induced osteoclast differentiation. Int J Mol Med. 33:178–184. 2014.PubMed/NCBI
14	Hodge G, Hodge S, Holmes-Liew CL, Reynolds PN and Holmes M: Loss of glucocorticoid receptor from pro-inflammatory T cells after lung transplant. J Heart Lung Transplant. 33:957–962. 2014. View Article : Google Scholar : PubMed/NCBI
15	Martinez-Schlurmann NI, Rampa S, Speicher DG and Allareddy V, Rotta AT and Allareddy V: Prevalence, predictors and outcomes of cardiopulmonary resuscitation in hospitalized adult stem cell transplant recipients in the United States: Not just opening the black box but exploring an opportunity to optimize! Bone Marrow Transplant. 50:1578–1581. 2015. View Article : Google Scholar : PubMed/NCBI
16	Sarmento CA, Rodrigues MN, Bocabello RZ, Mess AM and Miglino MA: Pilot study: Bone marrow stem cells as a treatment for dogs with chronic spinal cord injury. Regen Med Res. 2:92014. View Article : Google Scholar : PubMed/NCBI
17	Cho DI, Kim MR, Jeong HY, Jeong HC, Jeong MH, Yoon SH, Kim YS and Ahn Y: Mesenchymal stem cells reciprocally regulate the M1/M2 balance in mouse bone marrow-derived macrophages. Exp Mol Med. 46:e702014. View Article : Google Scholar : PubMed/NCBI
18	Wasnik S, Tiwari A, Kirkland MA and Pande G: Osteohematopoietic stem cell niches in bone marrow. Int Rev Cell Mol Biol. 298:95–133. 2012. View Article : Google Scholar : PubMed/NCBI
19	Rong JU, Wen Z, Rong WU and Zhichun F: Interaction between neural stem cells and bone marrow derived-mesenchymal stem cells during differentiation. Biomed Rep. 3:242–246. 2015.PubMed/NCBI
20	Chang J, Rimando A, Pallas M, Camins A, Porquet D, Reeves J, Shukitt-Hale B, Smith MA, Joseph JA and Casadesus G: Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer's disease. Neurobiol Aging. 33:2062–2071. 2012. View Article : Google Scholar : PubMed/NCBI
21	McCormack D and McFadden D: Pterostilbene and cancer: Current review. J Surg Res. 173:e53–e61. 2012. View Article : Google Scholar : PubMed/NCBI
22	Wang X, Xi WC and Wang F: The beneficial effects of intracoronary autologous bone marrow stem cell transfer as an adjunct to percutaneous coronary intervention in patients with acute myocardial infarction. Biotechnol Lett. 36:2163–2168. 2014. View Article : Google Scholar : PubMed/NCBI
23	Ma X, Choudhury SN, Hua X, Dai Z and Li Y: Interaction of the oncogenic miR-21 microRNA and the p53 tumor suppressor pathway. Carcinogenesis. 34:1216–1223. 2013. View Article : Google Scholar : PubMed/NCBI
24	Liu Y, Wang L, Fatahi R, Kronenberg M, Kalajzic I, Rowe D, Li Y and Maye P: Isolation of murine bone marrow derived mesenchymal stem cells using Twist2 Cre transgenic mice. Bone. 47:916–925. 2010. View Article : Google Scholar : PubMed/NCBI
25	Robitaille N, Lacroix J, Alexandrov L, Clayton L, Cortier M, Schultz KR, Bittencourt H and Duval M: Excess of veno-occlusive disease in a randomized clinical trial on a higher trigger for red blood cell transfusion after bone marrow transplantation: A canadian blood and marrow transplant group trial. Biol Blood Marrow Transplant. 19:468–473. 2013. View Article : Google Scholar : PubMed/NCBI
26	Haghpanah V, Fallah P, Tavakoli R, Naderi M, Samimi H, Soleimani M and Larijani B: Antisense-miR-21 enhances differentiation/apoptosis and reduces cancer stemness state on anaplastic thyroid cancer. Tumour Biol. Aug 20–2015.(Epub ahead of print). PubMed/NCBI
27	Wang C, Sun H, Song Y, Ma Z, Zhang G, Gu X and Zhao L: Pterostilbene attenuates inflammation in rat heart subjected to ischemia-reperfusion: Role of TLR4/NF-κB signaling pathway. Int J Clin Exp Med. 8:1737–1746. 2015.PubMed/NCBI
28	Cichocki M, Paluszczak J, Szaefer H, Piechowiak A, Rimando AM and Baer-Dubowska W: Pterostilbene is equally potent as resveratrol in inhibiting 12-O-tetradecanoylphorbol-13-acetate activated NκB, AP-1, COX-2, and iNOS in mouse epidermis. Mol Nutr Food Res. 52 Suppl 1:S62–S70. 2008.PubMed/NCBI
29	McCormack D and McFadden D: A review of pterostilbene antioxidant activity and disease modification. Oxid Med Cell Longev. 2013:5754822013. View Article : Google Scholar : PubMed/NCBI
30	Zaman MS, Shahryari V, Deng G, Thamminana S, Saini S, Majid S, Chang I, Hirata H, Ueno K, Yamamura S, et al: Up-regulation of microRNA-21 correlates with lower kidney cancer survival. PLoS One. 7:e310602012. View Article : Google Scholar : PubMed/NCBI