Skip to main content
Erschienen in: Medical Oncology 9/2014

01.09.2014 | Original Paper

Prognostic potential of microRNA-138 and its target mRNA PDK1 in sera for patients with non-small cell lung cancer

verfasst von: Lihong Han, Guoxiu Zhang, Nali Zhang, Haiyan Li, Yanyan Liu, Aiguo Fu, Youguang Zheng

Erschienen in: Medical Oncology | Ausgabe 9/2014

Einloggen, um Zugang zu erhalten

Abstract

microRNA (miR)-138 has been recognized as a potential tumor suppressor via regulating 3-phosphoinositide-dependent protein kinase-1 (PDK1) expression in non-small cell lung cancer (NSCLC) cells. The aim of this study was to investigate miR-138 and PDK1 mRNA expression in serum of NSCLC and their associations with patients’ prognosis. miR-138 and PDK1 mRNA expressions in 100 NSCLCs and 100 healthy control sera were detected by quantitative real-time PCR. miR-138 expression level was significantly lower in NSCLC serum samples than in healthy control serum samples (P < 0.001), while PDK1 mRNA expression level was significantly increased in NSCLC serum samples compared to healthy control serum samples (P < 0.001). In addition, miR-138 downregulation and PDK1 upregulation were both significantly associated with advanced tumor-node-metastasis (TNM) stage (both P = 0.002) and positive lymph node metastasis (both P = 0.01) of NSCLC patients. Moreover, the overall survival of NSCLC patients with low miR-138 expression or high PDK1 mRNA expression was obviously shorter than those with high miR-138 expression or low PDK1 mRNA expression (both P < 0.001). Notably, NSCLC patients with combined miR-138 downregulation and PDK1 upregulation (miR-138-low/PDK1-high) had shortest overall survival (P < 0.001). Furthermore, multivariate analysis showed that miR-138 expression (P = 0.01), PDK1 expression (P = 0.01), and combined expression of miR-138 and PDK1 (miR-138/PDK1, P = 0.001) were all independent prognostic factors for overall survival in NSCLC patients. Deregulation of miR-138/PDK1 cascade may be implicated in carcinogenesis and cancer progression of human NSCLC. More importantly, miR-138 and PDK1 may synergistically predict patients’ prognosis and their combination may represent a promising prognostic biomarker of human NSCLC.
Literatur
1.
Zurück zum Zitat Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.PubMedCrossRef Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.PubMedCrossRef
2.
Zurück zum Zitat López-González A, Millán PI, Cantos B, Provencio M. Surveillance of resected non-small cell lung cancer. Clin Transl Oncol. 2012;14:721–5.PubMedCrossRef López-González A, Millán PI, Cantos B, Provencio M. Surveillance of resected non-small cell lung cancer. Clin Transl Oncol. 2012;14:721–5.PubMedCrossRef
3.
Zurück zum Zitat Youlden DR, Cramb SM, Baade PD. The international epidemiology of lung cancer: geographical distribution and secular trends. J Thorac Oncol. 2008;3:819–31.PubMedCrossRef Youlden DR, Cramb SM, Baade PD. The international epidemiology of lung cancer: geographical distribution and secular trends. J Thorac Oncol. 2008;3:819–31.PubMedCrossRef
4.
Zurück zum Zitat Zarogoulidis K, Zarogoulidis P, Darwiche K, Boutsikou E, Machairiotis N, Tsakiridis K, et al. Treatment of non-small cell lung cancer (NSCLC). J Thorac Dis. 2013;5:S389–96.PubMedPubMedCentral Zarogoulidis K, Zarogoulidis P, Darwiche K, Boutsikou E, Machairiotis N, Tsakiridis K, et al. Treatment of non-small cell lung cancer (NSCLC). J Thorac Dis. 2013;5:S389–96.PubMedPubMedCentral
5.
Zurück zum Zitat Filipits M, Pirker R. Predictive markers in the adjuvant therapy of non-small cell lung cancer. Lung Cancer. 2011;74:355–63.PubMedCrossRef Filipits M, Pirker R. Predictive markers in the adjuvant therapy of non-small cell lung cancer. Lung Cancer. 2011;74:355–63.PubMedCrossRef
6.
7.
Zurück zum Zitat Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.PubMedCrossRef Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.PubMedCrossRef
8.
Zurück zum Zitat Li PY, He FC, Zhou GQ. Association of human microRNA related genetic variations with cancer. Yi Chuan. 2011;33:870–8.PubMedCrossRef Li PY, He FC, Zhou GQ. Association of human microRNA related genetic variations with cancer. Yi Chuan. 2011;33:870–8.PubMedCrossRef
9.
Zurück zum Zitat Zhang H, Li W, Nan F, Ren F, Wang H, Xu Y, Zhang F. MicroRNA expression profile of colon cancer stem-like cells in HT29 adenocarcinoma cell line. Biochem Biophys Res Commun. 2011;404:273–8.PubMedCrossRef Zhang H, Li W, Nan F, Ren F, Wang H, Xu Y, Zhang F. MicroRNA expression profile of colon cancer stem-like cells in HT29 adenocarcinoma cell line. Biochem Biophys Res Commun. 2011;404:273–8.PubMedCrossRef
10.
Zurück zum Zitat de Krijger I, Mekenkamp LJ, Punt CJ, Nagtegaal ID. MicroRNAs in colorectal cancer metastasis. J Pathol. 2011;224:438–47.PubMedCrossRef de Krijger I, Mekenkamp LJ, Punt CJ, Nagtegaal ID. MicroRNAs in colorectal cancer metastasis. J Pathol. 2011;224:438–47.PubMedCrossRef
12.
Zurück zum Zitat Baffa R, Fassan M, Volinia S, O’Hara B, Liu CG, Palazzo JP, et al. MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets. J Pathol. 2009;219:214–21.PubMedCrossRef Baffa R, Fassan M, Volinia S, O’Hara B, Liu CG, Palazzo JP, et al. MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets. J Pathol. 2009;219:214–21.PubMedCrossRef
13.
Zurück zum Zitat Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. Identification of tissue-specific microRNAs from mouse. Curr Biol. 2002;12:735–9.PubMedCrossRef Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. Identification of tissue-specific microRNAs from mouse. Curr Biol. 2002;12:735–9.PubMedCrossRef
14.
Zurück zum Zitat Weber MJ. New human and mouse microRNA genes found by homology search. FEBS J. 2005;272:59–73.PubMedCrossRef Weber MJ. New human and mouse microRNA genes found by homology search. FEBS J. 2005;272:59–73.PubMedCrossRef
16.
Zurück zum Zitat Jin Y, Wang C, Liu X, Mu W, Chen Z, Yu D, Wang A, Dai Y, Zhou X. Molecular characterization of the microRNA-138-Fos-like antigen 1 (FOSL1) regulatory module in squamous cell carcinoma. J Biol Chem. 2011;286:40104–9.PubMedCrossRefPubMedCentral Jin Y, Wang C, Liu X, Mu W, Chen Z, Yu D, Wang A, Dai Y, Zhou X. Molecular characterization of the microRNA-138-Fos-like antigen 1 (FOSL1) regulatory module in squamous cell carcinoma. J Biol Chem. 2011;286:40104–9.PubMedCrossRefPubMedCentral
17.
Zurück zum Zitat Qiu S, Huang D, Yin D, Li F, Li X, Kung HF, Peng Y. Suppression of tumorigenicity by microRNA-138 through inhibition of EZH2-CDK4/6-pRb-E2F1 signal loop in glioblastoma multiforme. Biochim Biophys Acta. 2013;1832:1697–707.PubMedCrossRef Qiu S, Huang D, Yin D, Li F, Li X, Kung HF, Peng Y. Suppression of tumorigenicity by microRNA-138 through inhibition of EZH2-CDK4/6-pRb-E2F1 signal loop in glioblastoma multiforme. Biochim Biophys Acta. 2013;1832:1697–707.PubMedCrossRef
18.
Zurück zum Zitat Jin Y, Chen D, Cabay RJ, Wang A, Crowe DL, Zhou X. Role of microRNA-138 as a potential tumor suppressor in head and neck squamous cell carcinoma. Int Rev Cell Mol Biol. 2013;303:357–85.PubMedCrossRefPubMedCentral Jin Y, Chen D, Cabay RJ, Wang A, Crowe DL, Zhou X. Role of microRNA-138 as a potential tumor suppressor in head and neck squamous cell carcinoma. Int Rev Cell Mol Biol. 2013;303:357–85.PubMedCrossRefPubMedCentral
19.
Zurück zum Zitat Liu X, Wang C, Chen Z, Jin Y, Wang Y, Kolokythas A, Dai Y, Zhou X. MicroRNA-138 suppresses epithelial-mesenchymal transition in squamous cell carcinoma cell lines. Biochem J. 2011;440:23–31.PubMedCrossRefPubMedCentral Liu X, Wang C, Chen Z, Jin Y, Wang Y, Kolokythas A, Dai Y, Zhou X. MicroRNA-138 suppresses epithelial-mesenchymal transition in squamous cell carcinoma cell lines. Biochem J. 2011;440:23–31.PubMedCrossRefPubMedCentral
20.
Zurück zum Zitat Wang Q, Zhong M, Liu W, Li J, Huang J, Zheng L. Alterations of microRNAs in cisplatin-resistant human non-small cell lung cancer cells (A549/DDP). Exp Lung Res. 2011;37:427–34.PubMedCrossRef Wang Q, Zhong M, Liu W, Li J, Huang J, Zheng L. Alterations of microRNAs in cisplatin-resistant human non-small cell lung cancer cells (A549/DDP). Exp Lung Res. 2011;37:427–34.PubMedCrossRef
21.
Zurück zum Zitat Wang Q, Tang H, Yin S, Dong C. Downregulation of microRNA-138 enhances the proliferation, migration and invasion of cholangiocarcinoma cells through the upregulation of RhoC/p-ERK/MMP-2/MMP-9. Oncol Rep. 2013;29:2046–52.PubMed Wang Q, Tang H, Yin S, Dong C. Downregulation of microRNA-138 enhances the proliferation, migration and invasion of cholangiocarcinoma cells through the upregulation of RhoC/p-ERK/MMP-2/MMP-9. Oncol Rep. 2013;29:2046–52.PubMed
22.
Zurück zum Zitat Yeh YM, Chuang CM, Chao KC, Wang LH. MicroRNA-138 suppresses ovarian cancer cell invasion and metastasis by targeting SOX4 and HIF-1α. Int J Cancer. 2013;133:867–78.PubMedCrossRef Yeh YM, Chuang CM, Chao KC, Wang LH. MicroRNA-138 suppresses ovarian cancer cell invasion and metastasis by targeting SOX4 and HIF-1α. Int J Cancer. 2013;133:867–78.PubMedCrossRef
23.
Zurück zum Zitat Zhang H, Zhang H, Zhao M, Lv Z, Zhang X, Qin X, Wang H, Wang S, Su J, Lv X, Liu H, Du W, Zhou W, Chen X, Fei K. MiR-138 inhibits tumor growth through repression of EZH2 in non-small cell lung cancer. Cell Physiol Biochem. 2013;31:56–65.PubMedCrossRef Zhang H, Zhang H, Zhao M, Lv Z, Zhang X, Qin X, Wang H, Wang S, Su J, Lv X, Liu H, Du W, Zhou W, Chen X, Fei K. MiR-138 inhibits tumor growth through repression of EZH2 in non-small cell lung cancer. Cell Physiol Biochem. 2013;31:56–65.PubMedCrossRef
24.
Zurück zum Zitat Yang H, Tang Y, Guo W, Du Y, Wang Y, Li P, Zang W, Yin X, Wang H, Chu H, Zhang G, Zhao G. Up-regulation of microRNA-138 induce radiosensitization in lung cancer cells. Tumor Biol. 2014;35:6557–65. Yang H, Tang Y, Guo W, Du Y, Wang Y, Li P, Zang W, Yin X, Wang H, Chu H, Zhang G, Zhao G. Up-regulation of microRNA-138 induce radiosensitization in lung cancer cells. Tumor Biol. 2014;35:6557–65.
25.
Zurück zum Zitat Ye XW, Yu H, Jin YK, Jing XT, Xu M, Wan ZF, Zhang XY. miR-138 inhibits proliferation by targeting 3-phosphoinositide-dependent protein kinase-1 in non-small cell lung cancer cells. Clin Respir J. 2014. doi:10.1111/crj.12100. Ye XW, Yu H, Jin YK, Jing XT, Xu M, Wan ZF, Zhang XY. miR-138 inhibits proliferation by targeting 3-phosphoinositide-dependent protein kinase-1 in non-small cell lung cancer cells. Clin Respir J. 2014. doi:10.​1111/​crj.​12100.
26.
Zurück zum Zitat Liu X, Lv XB, Wang XP, Sang Y, Xu S, Hu K, Wu M, Liang Y, Liu P, Tang J, Lu WH, Feng QS, Chen LZ, Qian CN, Bei JX, Kang T, Zeng YX. MiR-138 suppressed nasopharyngeal carcinoma growth and tumorigenesis by targeting the CCND1 oncogene. Cell Cycle. 2012;11:2495–506.PubMedCrossRef Liu X, Lv XB, Wang XP, Sang Y, Xu S, Hu K, Wu M, Liang Y, Liu P, Tang J, Lu WH, Feng QS, Chen LZ, Qian CN, Bei JX, Kang T, Zeng YX. MiR-138 suppressed nasopharyngeal carcinoma growth and tumorigenesis by targeting the CCND1 oncogene. Cell Cycle. 2012;11:2495–506.PubMedCrossRef
27.
Zurück zum Zitat Long L, Huang G, Zhu H, Guo Y, Liu Y, Huo J. Down-regulation of miR-138 promotes colorectal cancer metastasis via directly targeting TWIST2. J Transl Med. 2013;11:275.PubMedCrossRef Long L, Huang G, Zhu H, Guo Y, Liu Y, Huo J. Down-regulation of miR-138 promotes colorectal cancer metastasis via directly targeting TWIST2. J Transl Med. 2013;11:275.PubMedCrossRef
28.
Zurück zum Zitat Medina JR. Selective 3-phosphoinositide-dependent kinase 1 (PDK1) inhibitors: dissecting the function and pharmacology of PDK1. J Med Chem. 2013;56:2726–37.PubMedCrossRef Medina JR. Selective 3-phosphoinositide-dependent kinase 1 (PDK1) inhibitors: dissecting the function and pharmacology of PDK1. J Med Chem. 2013;56:2726–37.PubMedCrossRef
29.
Zurück zum Zitat Bayascas JR. PDK1: the major transducer of PI 3-kinase actions. Curr Top Microbiol Immunol. 2010;346:9–29.PubMed Bayascas JR. PDK1: the major transducer of PI 3-kinase actions. Curr Top Microbiol Immunol. 2010;346:9–29.PubMed
30.
31.
Zurück zum Zitat Li Y, Yang KJ, Park J. Multiple implications of 3-phosphoinositide-dependent protein kinase 1 in human cancer. World J Biol Chem. 2010;1:239–47.PubMedCrossRefPubMedCentral Li Y, Yang KJ, Park J. Multiple implications of 3-phosphoinositide-dependent protein kinase 1 in human cancer. World J Biol Chem. 2010;1:239–47.PubMedCrossRefPubMedCentral
32.
Zurück zum Zitat Bayascas JR, Leslie NR, Parsons R, Fleming S, Alessi DR. Hypomorphic mutation of PDK1 suppresses tumorigenesis in PTEN(±) mice. Curr Biol. 2005;15:1839–46.PubMedCrossRef Bayascas JR, Leslie NR, Parsons R, Fleming S, Alessi DR. Hypomorphic mutation of PDK1 suppresses tumorigenesis in PTEN(±) mice. Curr Biol. 2005;15:1839–46.PubMedCrossRef
33.
Zurück zum Zitat Yu J, Chen KS, Li YN, Yang J, Zhao L. Silencing of PDK1 gene expression by RNA interference suppresses growth of esophageal cancer. Asian Pac J Cancer Prev. 2012;13:4147–51.PubMedCrossRef Yu J, Chen KS, Li YN, Yang J, Zhao L. Silencing of PDK1 gene expression by RNA interference suppresses growth of esophageal cancer. Asian Pac J Cancer Prev. 2012;13:4147–51.PubMedCrossRef
34.
Zurück zum Zitat Liu Y, Wang J, Wu M, Wan W, Sun R, Yang D, Sun X, Ma D, Ying G, Zhang N. Down-regulation of 3-phosphoinositide-dependent protein kinase-1 levels inhibits migration and experimental metastasis of human breast cancer cells. Mol Cancer Res. 2009;7:944–54.PubMedCrossRef Liu Y, Wang J, Wu M, Wan W, Sun R, Yang D, Sun X, Ma D, Ying G, Zhang N. Down-regulation of 3-phosphoinositide-dependent protein kinase-1 levels inhibits migration and experimental metastasis of human breast cancer cells. Mol Cancer Res. 2009;7:944–54.PubMedCrossRef
Metadaten
Titel
Prognostic potential of microRNA-138 and its target mRNA PDK1 in sera for patients with non-small cell lung cancer
verfasst von
Lihong Han
Guoxiu Zhang
Nali Zhang
Haiyan Li
Yanyan Liu
Aiguo Fu
Youguang Zheng
Publikationsdatum
01.09.2014
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 9/2014
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0129-y

Weitere Artikel der Ausgabe 9/2014

Medical Oncology 9/2014 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.