MicroRNA-182 modulates chemosensitivity of human non-small cell lung cancer to cisplatin by targeting PDCD4

Diagnostic Pathology

Shao-shui Chen¹  Yan-zhang Hao¹  Ze-shun Yu¹  Mian-li Li¹  Feng Wang¹  Fang-ling Ning¹ 

[1] Department of Oncology, Binzhou Medical College Affiliated Hospital, 661#, Yellow-River Second Street, 256603 Binzhou, Shandong Province, China

关键词: NSCLC;    A549;    Chemosensitivity;    miR-182;    PDCD4;    miRNA;   

Others  :  870266
DOI  :  10.1186/1746-1596-9-143

 received in 2014-05-19, accepted in 2014-06-22,  发布年份 2014

【 摘 要 】

Background

Overexpression of microRNA-182 (miR-182) is found in various human cancers, including non-small cell lung cancer (NSCLC). Our aim is to investigate the association of miR-182 expression with the sensitivity of NSCLC to cisplatin.

Methods

TaqMan RT-PCR or Western blot assay was performed to detect the expression of mature miR-182 and programmed cell death 4 (PDCD4) protein. miR-182 and (or) PDCD4 depleted cell lines were generated using miR-182 inhibitor and (or) siRNA. The viabilities of treated cells were analyzed using MTT assay.

Results

The expression level of miR-182 in A549 cell line was significantly higher than that in NHBE cell line (p < 0.01). Transfection of miR-182 inhibitor induced sensitivity of A549 cells to cisplatin. A549 cells transfected with PDCD4 siRNA became more resistant to cisplatin therapy. We found an increase PDCD4 protein level following the transfection of miR-182 inhibitor using Western blot analysis. In addition, the enhanced growth-inhibitory effect by miR-182 inhibitor was weakened after the addition of PDCD4 siRNA.

Conclusions

The results of the present study demonstrated that overexpression of miR-182 may involve in chemoresistance of NSCLC cells to cisplatin by down-regulating PDCD4.

【 授权许可】

   
2014 Ning et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Siegel R, Ma J, Zou Z, Jemal A: Cancer statistics, 2014. CA Cancer J Clin 2014, 64(1):9-29.
• [2]Szakacs G, Paterson JK, Ludwig JA, Booth-Genthe C, Gottesman MM: Targeting multidrug resistance in cancer. Nat Rev Drug Discov 2006, 5(3):219-234.
• [3]Zheng S, Du Y, Chu H, Chen X, Li P, Wang Y, Ma Y, Wang H, Zang W, Zhang G, Zhao G: Analysis of MAT3 gene expression in NSCLC. Diagn Pathol 2013, 8:166.
• [4]Lu Q, Lu S, Huang L, Wang T, Wan Y, Zhou CX, Zhang C, Zhang Z, Li X: The expression of V-ATPase is associated with drug resistance and pathology of non-small-cell lung cancer. Diagn Pathol 2013, 8:145.
• [5]van Kouwenhove M, Kedde M, Agami R: MicroRNA regulation by RNA-binding proteins and its implications for cancer. Nat Rev Cancer 2011, 11(9):644-656.
• [6]Calin GA, Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer 2006, 6(11):857-866.
• [7]Guan P, Yin Z, Li X, Wu W, Zhou B: Meta-analysis of human lung cancer microRNA expression profiling studies comparing cancer tissues with normal tissues. J Exp Clin Cancer Res 2012, 31:54.
• [8]Yang WB, Chen PH, Hsu TS, Fu TF, Su WC, Liaw H, Chang WC, Hung JJ: Sp1-mediated microRNA-182 expression regulates lung cancer progression. Oncotarget 2014, 5(3):740-753.
• [9]Wang M, Wang Y, Zang W, Wang H, Chu H, Li P, Li M, Zhang G, Zhao G: Downregulation of microRNA-182 inhibits cell growth and invasion by targeting programmed cell death 4 in human lung adenocarcinoma cells. Tumour Biol 2014, 35(1):39-46.
• [10]Husted S, Sokilde R, Rask L, Cirera S, Busk PK, Eriksen J, Litman T: MicroRNA expression profiles associated with development of drug resistance in Ehrlich ascites tumor cells. Mol Pharm 2011, 8(6):2055-2062.
• [11]Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S, Allgayer H: MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 2008, 27(15):2128-2136.
• [12]Wang YQ, Guo RD, Guo RM, Sheng W, Yin LR: MicroRNA-182 promotes cell growth, invasion, and chemoresistance by targeting programmed cell death 4 (PDCD4) in human ovarian carcinomas. J Cell Biochem 2013, 114(7):1464-1473.
• [13]Zhu S, Wu H, Wu F, Nie D, Sheng S, Mo YY: MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res 2008, 18(3):350-359.
• [14]Judson I, Kelland LR: New developments and approaches in the platinum arena. Drugs 2000, 59(Suppl 4):29-36. discussion 37-28
• [15]Reed JC: Mechanisms of apoptosis avoidance in cancer. Curr Opin Oncol 1999, 11(1):68-75.
• [16]Meng F, Glaser SS, Francis H, DeMorrow S, Han Y, Passarini JD, Stokes A, Cleary JP, Liu X, Venter J, Kumar P, Priester S, Hubble L, Staloch D, Sharma J, Liu CG, Alpini G: Functional analysis of microRNAs in human hepatocellular cancer stem cells. J Cell Mol Med 2012, 16(1):160-173.
• [17]Farazi TA, Spitzer JI, Morozov P, Tuschl T: miRNAs in human cancer. J Pathol 2011, 223(2):102-115.
• [18]Shah AA, Leidinger P, Blin N, Meese E: miRNA: small molecules as potential novel biomarkers in cancer. Curr Med Chem 2010, 17(36):4427-4432.
• [19]Jiang L, Mao P, Song L, Wu J, Huang J, Lin C, Yuan J, Qu L, Cheng SY, Li J: miR-182 as a prognostic marker for glioma progression and patient survival. Am J Pathol 2010, 177(1):29-38.
• [20]Segura MF, Hanniford D, Menendez S, Reavie L, Zou X, Alvarez-Diaz S, Zakrzewski J, Blochin E, Rose A, Bogunovic D, Polsky D, Wei J, Lee P, Belitskaya-Levy I, Bhardwaj N, Osman I, Hernando E: Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor. Proc Natl Acad Sci USA 2009, 106(6):1814-1819.
• [21]Tang T, Wong HK, Gu W, Yu MY, To KF, Wang CC, Wong YF, Cheung TH, Chung TK, Choy KW: MicroRNA-182 plays an onco-miRNA role in cervical cancer. Gynecol Oncol 2013, 129(1):199-208.
• [22]Moskwa P, Buffa FM, Pan Y, Panchakshari R, Gottipati P, Muschel RJ, Beech J, Kulshrestha R, Abdelmohsen K, Weinstock DM, Gorospe M, Harris AL, Helleday T, Chowdhury D: miR-182-mediated downregulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitors. Mol Cell 2011, 41(2):210-220.
• [23]Qiu T, Zhou L, Wang T, Xu J, Wang J, Chen W, Zhou X, Huang Z, Zhu W, Shu Y, Liu P: miR-503 regulates the resistance of non-small cell lung cancer cells to cisplatin by targeting Bcl-2. Int J Mol Med 2013, 32(3):593-598.
• [24]Gao W, Lu X, Liu L, Xu J, Feng D, Shu Y: MiRNA-21: a biomarker predictive for platinum-based adjuvant chemotherapy response in patients with non-small cell lung cancer. Cancer Biol Ther 2012, 13(5):330-340.
• [25]Galluzzi L, Morselli E, Vitale I, Kepp O, Senovilla L, Criollo A, Servant N, Paccard C, Hupe P, Robert T, Ripoche H, Lazar V, Harel-Bellan A, Dessen P, Barillot E, Kroemer G: miR-181a and miR-630 regulate cisplatin-induced cancer cell death. Cancer Res 2010, 70(5):1793-1803.
• [26]Cho HM, Jeon HS, Lee SY, Jeong KJ, Park SY, Lee HY, Lee JU, Kim JH, Kwon SJ, Choi E, Na MJ, Kang J, Son JW: microRNA-101 inhibits lung cancer invasion through the regulation of enhancer of zeste homolog 2. Exp Ther Med 2011, 2(5):963-967.
• [27]Kang J, Lee SY, Lee SY, Kim YJ, Park JY, Kwon SJ, Na MJ, Lee EJ, Jeon HS, Son JW: microRNA-99b acts as a tumor suppressor in non-small cell lung cancer by directly targeting fibroblast growth factor receptor 3. Exp Ther Med 2012, 3(1):149-153.
• [28]Liu XH, Lu KH, Wang KM, Sun M, Zhang EB, Yang JS, Yin DD, Liu ZL, Zhou J, Liu ZJ, De W, Wang ZX: MicroRNA-196a promotes non-small cell lung cancer cell proliferation and invasion through targeting HOXA5. BMC Cancer 2012, 12:348.
• [29]Feng S, Cong S, Zhang X, Bao X, Wang W, Li H, Wang Z, Wang G, Xu J, Du B, Qu D, Xiong W, Yin M, Ren X, Wang F, He J, Zhang B: MicroRNA-192 targeting retinoblastoma 1 inhibits cell proliferation and induces cell apoptosis in lung cancer cells. Nucleic Acids Res 2011, 39(15):6669-6678.
• [30]Xiong S, Zheng Y, Jiang P, Liu R, Liu X, Chu Y: MicroRNA-7 inhibits the growth of human non-small cell lung cancer A549 cells through targeting BCL-2. Int J Biol Sci 2011, 7(6):805-814.