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Clinical and Translational Oncology
Published in: Clinical and Translational Oncology 4/2016

01-04-2016 | Research Article

Association between downexpression of MiR-203 and poor prognosis in non-small cell lung cancer patients

Authors: R. Tang, T. Zhong, Y. Dang, X. Zhang, P. Li, G. Chen

Published in: Clinical and Translational Oncology | Issue 4/2016

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Abstract

Background and aim

Although miR-203 has been proposed as a relevant biomarker for several cancers, the validated prognostic significance of miR-203 in lung cancer remains obscure. Thus, we aimed to identify the relationship between miR-203 expression and clinicopathological significance in non-small cell lung cancer (NSCLC) patients in the current study.

Methods

The expression of miR-203 in 125 cases of NSCLC and their paired adjacent non-cancerous tissues was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Simultaneously, the correlation of miR-203 expression with a variety of clinicopathological factors and patient survival was analyzed. Functionally, in vitro effects of miR-203 on proliferation and viability were explored in lung cancer H460, A549, H1299, PC9 and H292 cells, as assessed by MTS tetrazolium assay and fluorimetric resorufin viability assay, respectively.

Results

The relative level of miR-203 was 6.12 ± 6.25 in NSCLC tissues, remarkably downregulated than that of their paired non-tumorous lung tissues (7.88 ± 5.56, P = 0.019). The area under curve (AUC) of low expression of miR-203 to diagnose NSCLC was 0.622 (95 % CI 0.552–0.692, P = 0.001). MiR-203 expression was negatively correlated to lymphatic metastasis (r = −0.334, P < 0.001), tumor size (r = −0.407, P < 0.001) and clinical TNM stages (r = −0.298, P = 0.001). Furthermore, the survival of the low miR-203 expression group was 4.88 ± 4.38 months, markedly shorter than that of the high expression group (23.35 ± 1.12 months, P < 0.001). The level of miR-203 was an independent prognostic indicator of NSCLC using univariate analysis. MiR-203 mimic could suppress the cell growth of five lung cancer cell lines tested to different degrees in vitro.

Conclusions

MiR-203 could become a prognostic predictor in NSCLC and may be a new target for the molecular therapy of NSCLC patients.
Literature
1.
Lee PN, Forey BA. Indirectly estimated absolute lung cancer mortality rates by smoking status and histological type based on a systematic review. BMC Cancer. 2013;13:189.CrossRefPubMedPubMedCentral
2.
Chen X, Liu Y, Roe OD, Qian Y, Guo R, Zhu L, et al. Gefitinib or erlotinib as maintenance therapy in patients with advanced stage non-small cell lung cancer: a systematic review. PLoS One. 2013;8(3):e59314.CrossRefPubMedPubMedCentral
3.
Brothers JF, Hijazi K, Mascaux C, El-Zein RA, Spitz MR, Spira A. Bridging the clinical gaps: genetic, epigenetic and transcriptomic biomarkers for the early detection of lung cancer in the post-National Lung Screening Trial era. BMC Med. 2013;11:168.CrossRefPubMedPubMedCentral
4.
Barrow TM, Michels KB. Epigenetic epidemiology of cancer. Biochem Biophys Res Commun. 2014;455(1–2):70–83.CrossRefPubMed
5.
Gazala S, Pelletier JS, Storie D, Johnson JA, Kutsogiannis DJ, Bedard EL. A systematic review and meta-analysis to assess patient-reported outcomes after lung cancer surgery. Sci World J. 2013;2013:789625.CrossRef
6.
Li S, Liu Z, Zhu F, Fan X, Wu X, Zhao H, et al. Curcumin lowers erlotinib resistance in non-small cell lung carcinoma cells with mutated EGF receptor. Oncol Res. 2013;21(3):137–44.CrossRefPubMed
7.
Roy M, Luo YH, Ye M, Liu J. Nonsmall cell lung cancer therapy: insight into multitargeted small-molecule growth factor receptor inhibitors. Biomed Res Int. 2013;2013:964743.CrossRefPubMedPubMedCentral
8.
9.
Ramshankar V, Krishnamurthy A. Lung cancer detection by screening—presenting circulating miRNAs as a promising next generation biomarker breakthrough. Asian Pac J Cancer Prev APJCP. 2013;14(4):2167–72.CrossRefPubMed
10.
Verderio P, Bottelli S, Ciniselli CM, Pierotti MA, Gariboldi M, Pizzamiglio S. NqA: an R-based algorithm for the normalization and analysis of microRNA quantitative real-time polymerase chain reaction data. Anal Biochem. 2014;461:7–9.CrossRefPubMed
11.
Ritchie W, Rasko JE. Refining microRNA target predictions: sorting the wheat from the chaff. Biochem Biophys Res Commun. 2014;445(4):780–4.CrossRefPubMed
12.
13.
Chen Z, Xu L, Ye X, Shen S, Li Z, Niu X, et al. Polymorphisms of microRNA sequences or binding sites and lung cancer: a meta-analysis and systematic review. PLoS One. 2013;8(4):e61008.CrossRefPubMedPubMedCentral
14.
15.
Gu J, Wang Y, Wu X. MicroRNA in the pathogenesis and prognosis of esophageal cancer. Curr Pharm Des. 2013;19(7):1292–300.PubMed
16.
Tian L, Li M, Ge J, Guo Y, Sun Y, Liu M, et al. MiR-203 is downregulated in laryngeal squamous cell carcinoma and can suppress proliferation and induce apoptosis of tumours. Tumour Biol J Int Soc for Oncodev Biol Med. 2014;35(6):5953–63.CrossRef
17.
Yu J, Li A, Hong SM, Hruban RH, Goggins M. MicroRNA alterations of pancreatic intraepithelial neoplasias. Clin Cancer Res Off J Am Assoc Cancer Res. 2012;18(4):981–92.CrossRef
18.
Gocze K, Gombos K, Juhasz K, Kovacs K, Kajtar B, Benczik M, et al. Unique microRNA expression profiles in cervical cancer. Anticancer Res. 2013;33(6):2561–7.PubMed
19.
Sonkoly E, Loven J, Xu N, Meisgen F, Wei T, Brodin P, et al. MicroRNA-203 functions as a tumor suppressor in basal cell carcinoma. Oncogenesis. 2012;1:e3.CrossRefPubMedPubMedCentral
20.
Siu MK, Abou-Kheir W, Yin JJ, Chang YS, Barrett B, Suau F, et al. Loss of EGFR signaling regulated miR-203 promotes prostate cancer bone metastasis and tyrosine kinase inhibitors resistance. Oncotarget. 2014;5(11):3770–84.CrossRefPubMedPubMedCentral
21.
Chen G, Kronenberger P, Teugels E, De Greve J. Influence of RT-qPCR primer position on EGFR interference efficacy in lung cancer cells. Biol Proced Online. 2011;13:1.CrossRefPubMedCentral
22.
Chen G, Kronenberger P, Teugels E, Umelo IA, De Greve J. Targeting the epidermal growth factor receptor in non-small cell lung cancer cells: the effect of combining RNA interference with tyrosine kinase inhibitors or cetuximab. BMC Med. 2012;10:28.CrossRefPubMedPubMedCentral
23.
Chen G, Kronenberger P, Teugels E, Umelo IA, De Greve J. Effect of siRNAs targeting the EGFR T790 M mutation in a non-small cell lung cancer cell line resistant to EGFR tyrosine kinase inhibitors and combination with various agents. Biochem Biophys Res Commun. 2013;431(3):623–9.CrossRefPubMed
24.
Chen G, Kronenberger P, Umelo IA, Teugels E, De Greve J. Quantification of epidermal growth factor receptor T790M mutant transcripts in lung cancer cells by real-time reverse transcriptase-quantitative polymerase chain reaction. Anal Biochem. 2010;398(2):266–8.CrossRefPubMed
25.
Chen G, Noor A, Kronenberger P, Teugels E, Umelo IA, De Greve J. Synergistic effect of afatinib with su11274 in non-small cell lung cancer cells resistant to gefitinib or erlotinib. PLoS One. 2013;8(3):e59708.CrossRefPubMedPubMedCentral
26.
Chen G, Umelo IA, Lv S, Teugels E, Fostier K, Kronenberger P, et al. miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells. PLoS One. 2013;8(3):e60317.CrossRefPubMedPubMedCentral
27.
Rong M, He R, Dang Y, Chen G. Expression and clinicopathological significance of miR-146a in hepatocellular carcinoma tissues. Upsala J Med Sci. 2014;119(1):19–24.CrossRefPubMedPubMedCentral
28.
Albertini MC, Olivieri F, Lazzarini R, Pilolli F, Galli F, Spada G, et al. Predicting microRNA modulation in human prostate cancer using a simple String IDentifier (SID1.0). J Biomed Inform. 2011;44(4):615–20.CrossRefPubMed
29.
Dang Y, Luo D, Rong M, Chen G. Underexpression of miR-34a in hepatocellular carcinoma and its contribution towards enhancement of proliferating inhibitory effects of agents targeting c-MET. PLoS One. 2013;8(4):e61054.CrossRefPubMedPubMedCentral
30.
Dang YW, Zeng J, He RQ, Rong MH, Luo DZ, Chen G. Effects of miR-152 on cell growth inhibition, motility suppression and apoptosis induction in hepatocellular carcinoma cells. Asian Pac J Cancer Prev APJCP. 2014;15(12):4969–76.CrossRefPubMed
31.
Jin J, Deng J, Wang F, Xia X, Qiu T, Lu W, et al. The expression and function of microRNA-203 in lung cancer. Tumour Biol J Int Soc for Oncodev Biol Med. 2013;34(1):349–57.CrossRef
32.
Wang C, Wang X, Liang H, Wang T, Yan X, Cao M, et al. miR-203 inhibits cell proliferation and migration of lung cancer cells by targeting PKCalpha. PLoS One. 2013;8(9):e73985.CrossRefPubMedPubMedCentral
33.
Wang N, Liang H, Zhou Y, Wang C, Zhang S, Pan Y, et al. miR-203 suppresses the proliferation and migration and promotes the apoptosis of lung cancer cells by targeting SRC. PLoS One. 2014;9(8):e105570.CrossRefPubMedPubMedCentral
34.
Benaich N, Woodhouse S, Goldie SJ, Mishra A, Quist SR, Watt FM. Rewiring of an epithelial differentiation factor, miR-203, to inhibit human squamous cell carcinoma metastasis. Cell Rep. 2014;9(1):104–17.CrossRefPubMedPubMedCentral
35.
Wairagu PM, Park KH, Kim J, Choi JW, Kim HW, Yeh BI, et al. Combined therapeutic potential of nuclear receptors with receptor tyrosine kinase inhibitors in lung cancer. Biochem Biophys Res Commun. 2014;447(3):490–5.CrossRefPubMed
36.
Soma S, Tsuta K, Takano T, Hatanaka Y, Yoshida A, Suzuki K, et al. Intratumoral distribution of EGFR-amplified and EGFR-mutated cells in pulmonary adenocarcinoma. Pathol Res Pract. 2014;210(3):155–60.CrossRefPubMed
37.
Garofalo M, Romano G, Di Leva G, Nuovo G, Jeon YJ, Ngankeu A, et al. EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers. Nat Med. 2012;18(1):74–82.PubMedCentral
Metadata
Title
Association between downexpression of MiR-203 and poor prognosis in non-small cell lung cancer patients
Authors
R. Tang
T. Zhong
Y. Dang
X. Zhang
P. Li
G. Chen
Publication date
01-04-2016
Publisher
Springer Milan
Published in
Clinical and Translational Oncology / Issue 4/2016
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-015-1377-9

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