Department of Oncology,Nanyang Central Hospital,Zhengzhou University,Nanyang 473009,China (Zhang JW,Ren ZH);Nayang Medical College in Heman,Nayang 473000,China (Duan DM);Department of Oncology,First Affiliated Hospital of PLA General Hospital,Beijing 100048,China (Sun JZ)
Objective The purpose of this study is to investigate the effect of miR-449a on pancreatic cancer cells and the molecular mechanism. Methods The expression levels of miR-449a in pancreatic cancer cells treated or untreated with radiation was detected by qRT-PCR.High expression of miR-449a was achieved by transfecting miR-449a mimics into SW1990 cells. The cell growth,apoptosis and colony formation ability was assessed by MTT assay,flow cytometry and colony formation assay,respectively. The relationship of miR-449a and Cyclin D1 was determined by the TargetScan and dual luciferase reporter. Immunohistochemistry was used to examine protein levels of Cyclin D1 in pancreatic cancer and normal pancreas tissues. Si-Cyclin D1 was used to detecte the effect of Cyclin D1 on radiosensitivity of pancreatic cancer cells. Resutls The expression levels of miR-449a in pancreatic cancer cells with radiation treatment were decreased significantly. Mir-449a mimics increased the cell proliferation rates and apoptosis rates obviously,and decreased the colony formation ability in SW1990 cells treated with radiation. Resutls from the TargetScan and dual luciferase reporter showed that Cyclin D1 was the target of miR-449a. The positive staining rates of Cyclin D1 in pancreatic cancer tissue (85.7%,30/35) was higher than those in normal pancreas tissue (20%,2/10).Knockdown of Cyclin D1 enhanced the radiosensitivity of pancreatic cancer cells. Conclusion MiR-449a enhances the radiosensitivity of pancreatic cancer cells by targeting Cyclin D1.
Zhang Jingwei,Duan Dongmei,Sun Junzhong et al. Effect of miR-449a on radiosensitivity of pancreatic cancer cells[J]. Chinese Journal of Radiation Oncology, 2017, 26(11): 1332-1335.
[1] Siegel R,Naishadham D,Jemal A.Cancer statistics,2012[J].Cancer J Clin,2012,62(1):10-29.DOI:10.3322/caac.20138.
[2] Jacobs NL,Que FG,Miller RC,et al. Cumulative morbidity and late mortality in long-term survivors of exocrine pancreas cancer[J].J Gastrointest Cancer,2009,40(1-2):46-50.DOI:10.1007/s12029-009-9082-y.
[3] Spinelli GP,Zullo A,Romiti A,et al. Long-term survival in metastatic pancreatic cancer. A case report and review of the literature[J].JOP,2006,7(5):486-491.
[4] Li DH,Xie KP,Wolff R,et al. Pancreatic cancer[J].Lancet,2004,363(9414):1049-1057.DOI:10.1016/S0140-6736(04)15841-8.
[5] Gregory RI,Chendrimada TP,Cooch N,et al. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing[J].Cell,2005,123(4):631-640.DOI:10.1016/j.cell.2005.10.022.
[6] Lai EC.Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation[J].Nat Genet,2002,30(4):363-364.DOI:10.1038/ng865.
[7] Calin GA,Croce CM.MicroRNA signatures in human cancers[J].Nat Rev Cancer,2006,6(11):857-866.DOI:10.1038/nrc1997.
[8] Croce CM.Causes and consequences of microRNA dysregulation in cancer[J].Nat Rev Genet,2009,10(10):704-714.DOI:10.1038/nrg2634.
[9] Ueda T,Volinia S,Okumura H,et al. Relation between microRNA expression and progression and prognosis of gastric cancer:a microRNA expression analysis[J].Lancet Oncol,2010,11(2):136-146.DOI:10.1016/S1470-2045(09)70343-2.
[10] Gallinas SC,Lizé M.MIR449A (microRNA 449a)[J].Atlas Genet Cytogenet Oncol Haematol,2013,17(3):188-192.
[11] Zhang YH,Wang QQ,Li H,et al.miR-124 radiosensitizes human esophageal cancer cell TE-1 by targeting CDK4[J].Genet Mol Res,2016,15(2).DOI:10.4238/gmr.15027893.
[12] Song L,Liu S,Zhang L,et al. MiR-21 modulates radiosensitivity of cervical cancer through inhibiting autophagy via the PTEN/Akt/HIF-1α feedback loop and the Akt-mTOR signaling pathway[J].Tumor Biol,2016,37(9):12161-12168.DOI:10.1007/s13277-016-5073-3.
[13] Liu G,Li Y,Gao X.Overexpression of microRNA-133b sensitizes non-small cell lung cancer cells to irradiation through the inhibition of glycolysis[J].Oncol Lett,2016,11(4):2903-2908.DOI:10.3892/ol.2016.4316.
[14] Mao AH,Zhao QY,Zhou X,et al. MicroRNA-449a enhances radiosensitivity by downregulation of c-Myc in prostate cancer cells[J].Sci Rep,2016,6:27346.DOI:10.1038/srep27346.
[15] Mao AH,Liu Y,Wang YL,et al.miR-449a enhances radiosensitivity through modulating pRb/E2F1 in prostate cancer cells[J].Tumor Biol,2016,37(4):4831-4840.
[16] Liu YJ,Lin YF,Chen YF,et al. MicroRNA-449a enhances radiosensitivity in CL1-0 lung adenocarcinoma cells[J].PLoS One,2013,8(4):e62383.DOI:10.1371/journal.pone.0062383.
[17] Matsushime H,Ewen ME,Strom DK,et al. Identification and properties of an atypical catalytic subunit (p34PSK-J3/cdk4) for mammalian D type G1 cyclins[J].Cell,1992,71(2):323-334.DOI:10.1016/0092-8674(92)90360-O.
[18] Ajchenbaum F,Ando K,DeCaprio J,et al. Independent regulation of human D-type cyclin gene expression during G1 phase in primary human T lymphocytes[J].J Biol Chem,1993,268(6):4113-4119.
[19] Fracchiolla NS,Pruneri G,Pignataro L,et al. Molecular and immunohistochemical analysis of the bcl-1/Cyclin D1 gene in laryngeal squamous cell carcinomas:correlation of protein expression with lymph node metastases and advanced clinical stage[J].Cancer,1997,79(6):1114-1121.DOI:10.1002/(SICI)1097-0142(19970315)79:6<1114::AID-CNCR9>3.3.CO;2-I.