|
|
Inhibition of apoptosis in pancreatic cancer cells by miR-181a targeting CARF gene |
LI Junjian, CHEN Gang, ZHU Qiandong, YU Zhengping. |
Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China |
|
Cite this article: |
LI Junjian,CHEN Gang,ZHU Qiandong, et al. Inhibition of apoptosis in pancreatic cancer cells by miR-181a targeting CARF gene[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2019, 49(3): 167-171.
|
|
Abstract Objective: To explore the possible relationship between miR-181a and its predicted target gene-CARF, and to investigate their roles in regulating proliferation/apoptosis of pancreatic carcinoma cells. Methods: The miR-181a expression of pancreatic tissues/cells was detected by real-time fluorescent quantitative PCR. The miR-181a level was down-regulated by miR-181a inhibitors, and the proliferation activity of pancreatic cancer cells was examined by MTT. A PGL-3 vector containing the 3’-UTR sequence of the CARF gene was established to observe the relationship of miR-181a and CARF revealed by Dual Luciferase Reporter Assay System. The miR-181a level was regulated by agonists and inhibitors. Western blot was used to detect the expression of CARF protein. Results: Compared with normal pancreatic tissues and cells, miR-181a expression of pancreatic cancer tissues/cells was significantly increased (P<0.05). MiR-181a inhibitors significantly reduced the level of miR-181a and decreased its proliferative activity obviously (P<0.05). The Dual Luciferase Reporter Assay System indicated that miR-181a was co-transfected with a vector containing the 3’-UTR sequence of CARF, which significantly reduced luciferase activity (P<0.05). There was significant negative correlation between CARF protein expression and miR-181a concentration in pancreatic cancer cells (P<0.05). Conclusion: MiR-181a in pancreatic cancer tissues and cells was significantly increased, and promoted the development of pancreatic cancer through down-regulating its target gene CARF to enhance cell proliferation.
|
Received: 29 September 2018
|
|
|
|
|
[1] 陈千杰, 张金三, 郭强, 等. YAP1基因敲除对胰腺癌L3.6细胞增殖及迁移能力的影响[J]. 温州医科大学学报, 2018, 48(6): 391-395, 400
[2] 陈辉, 王兆洪, 陈龙, 等. 吴茱萸碱对人胰腺癌SW1990细胞株体内外增殖及凋亡的影响[J]. 温州医科大学学报, 2017, 47(6): 431-434, 440.
[3] PORUK K E, FIRPO M A, ADLER D G, et al. Screening for pancreatic cancer: why, how, and who?[J]. Ann Surg, 2013, 257(1): 17-26.
[4] ULTIMO S, MARTELLI A M, ZAULI G, et al. Roles and clinical implications of microRNAs in acute lymphoblastic leukemia[J]. J Cell Physiol, 2018, 233(8): 5642-5654.
[5] CHEN E, XU X, LIU R, et al. Small but heavy role: micrornas in hepatocellular carcinoma progression[J]. Biomed Res Int, 2018, 2018: 6784607.
[6] YUAN H L, WANG T, ZHANG K H. MicroRNAs as potential biomarkers for diagnosis, therapy and prognosis of gastric cancer[J]. Onco Targets Ther, 2018 ,11: 3891-3900.
[7] MANSOORI B, MOHAMMADI A, SHIRJANG S. MicroRNAs in the diagnosis and treatment of cancer[J]. Immunol Invest, 2017, 46(8): 880-897.
[8] LI Y, KUSCU C, BANACH A, et al. MiR-181a-5p inhibits cancer cell migration and angiogenesis via downregulation of matrix metalloproteinase-14[J]. Cancer Res, 2015, 75(13): 2674-2685.
[9] BRÄUER-HARTMANN D, HARTMANN J U, WURM A A,
et al. PML/RARα-Regulated miR-181a/b cluster targets the tumor suppressor RASSF1A in acute promyelocytic leuke-mia[J]. Cancer Res, 2015, 75(16): 3411-3424.
[10] SRIVASTAVA S K, ARORA S, SINQH S, et al. Singh. MicroRNAs in pancreatic malignancy: progress and promises [J]. Cancer Lett, 2014, 347(2): 167-174.
[11] SINGH R, KALRA R S, HASAN K, et al. Molecular characterization of collaborator of ARF (CARF) as a DNA damage response and cell cycle checkpoint regulatory protein[J]. Exp Cell Res, 2014, 322(2): 324-334.
[12] CHEUNG C T, SINGH R, KALRA R S, et al. Collaborator of ARF (CARF) regulates proliferative fate of human cells by dose-dependent regulation of DNA damage signaling[J]. J Biol Chem, 2014, 289(26): 18258-18269.
[13] DI Leva G, GAROFALO M, CROCE C M. MicroRNAs in cancer[J]. Annu Rev Pathol, 2014, 9: 287-314.
[14] WANG H, LI X T, WU C, et al. miR-132 can inhibit glioma cells invasion and migration by target MMP16 in vitro[J]. Onco Targets Ther, 2015, 8: 3211-3218.
[15] PETROVIC N, ERGUN S. miRNAs as potential treatment targets and treatment options in cancer[J]. Mol Diagn Ther, 2018, 22(2): 157-168.
[16] CHEN S, ZHU J, YU F, et al. Combination of miRNA and RNA functions as potential biomarkers for gastric cancer[J]. Tumour Biol, 2015, 36(12): 9909-9918.
[17] HOSSEINAHLI N, AGHAPOUR M, DUIJF P H G, et al. Treating cancer with microRNA replacement therapy: A literature review[J]. J Cell Physiol, 2018, 233(8): 5574-5588. |
|
|
|