Generic placeholder image

Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Research Article

Mir-320b Inhibits Pancreatic Cancer Cell Proliferation by Targeting FOXM1

Author(s): Zhou Jingyang, Che Jinhui, Xu Lu, Yang Weizhong, Li Yunjiu, Wang Haihong* and Zhou Wuyuan*

Volume 22, Issue 8, 2021

Published on: 17 September, 2020

Page: [1106 - 1113] Pages: 8

DOI: 10.2174/1389201021999200917144704

Price: $65

Abstract

Background: Pancreatic Ductal Adenocarcinoma (PDAC) is the most common and deadly cancer. Surgical resection is the only possible cure for pancreatic cancer but often has a poor prognosis, and the role of adjuvant therapy is urgently explored.

Methods: MicroRNAs (miRNAs) play a very important role in tumorigenesis by regulating the target genes. In this study, we identified miR-320b lower-expressed in human pancreatic cancer tissues but relatively higher-expressed in the adjacent non-tumor tissues.

Results: Consistently, the expression of miR-320b in different pancreatic cancer cell lines was significantly lower than the normal pancreatic cells. In order to identify the effects of miR-320b on cell growth, we overexpressed miR-320b in PANC-1 and FG pancreatic cancer cell lines, CCK8 and BrdU incorporation assay results showed that miR-320b inhibited cell proliferation.

Discussion: We next predicted miR-320b targeted FOXM1 (Forkhead box protein M1) and identified the negative relationship between miR-320b and FOXM1. We also demonstrated that elevated miR- 320b expression inhibited tumor growth in vivo.

Conclusion: All of these results showed that miR-320b suppressed pancreatic cancer cell proliferation by targeting FOXM1, which might provide a new diagnostic marker for pancreatic cancer.

Keywords: MiR-320b, FOXM1, Pancreatic Ductal Adenocarcinoma (PDAC), cell proliferation, tumor growth, diagnostic marker.

Graphical Abstract

[1]
Ferlay, J.S.I. Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11., 2015, 136(5), E359-E386.
[2]
Higginson, J. Encyclopedia of Toxicology; 3rd ed.; Elsevier: 2014, pg, 5220..
[3]
Hidalgo, M.; Cascinu, S.; Kleeff, J.; Labianca, R.; Löhr, J.M.; Neoptolemos, J.; Real, F.X.; Van Laethem, J.L.; Heinemann, V. Addressing the challenges of pancreatic cancer: Future directions for improving outcomes. Pancreatology, 2015, 15(1), 8-18.
[http://dx.doi.org/10.1016/j.pan.2014.10.001] [PMID: 25547205]
[4]
Vincent, A. Pancreatic cancer. Lancet, 2011, 378(9791), 607-620.
[http://dx.doi.org/10.1016/S0140-6736(10)62307-0]
[5]
Gillen, S.; Schuster, T.; Meyer Zum Büschenfelde, C.; Friess, H.; Kleeff, J. Preoperative/neoadjuvant therapy in pancreatic cancer: A systematic review and meta-analysis of response and resection percentages. PLoS Med., 2010, 7(4), e1000267.
[http://dx.doi.org/10.1371/journal.pmed.1000267] [PMID: 20422030]
[6]
Huang, W.H.; Chuanming, F.; Yingfang, W.H. MiR-23a-5p inhibits cell proliferation and invasion in pancreatic ductal adenocarcinoma by suppressing ECM1 expression. Am. J. Transl. Res., 2019, 11, 2983-2994.
[7]
Jin, Z. miR3303p suppresses liver cancer cell migration by targeting MAP2K1. Oncol. Lett., 2019, 18(1), 314-320.
[http://dx.doi.org/10.3892/ol.2019.10280]
[8]
Caldas, C.; Brenton, J.D. Sizing up miRNAs as cancer genes. Nat. Med., 2005, 11(7), 712-714.
[9]
Yan, H.; Wu, J.; Liu, W.; Zuo, Y.; Chen, S.; Zhang, S.; Zeng, M.; Huang, W. MicroRNA-20a overexpression inhibited proliferation and metastasis of pancreatic carcinoma cells. Hum. Gene Ther., 2010, 21(12), 1723-1734.
[http://dx.doi.org/10.1089/hum.2010.061] [PMID: 20583868]
[10]
Garzon, R.; Calin, G.A.; Croce, C.M. MicroRNAs in cancer. Annu. Rev. Med., 2009, 60(1), 167-179.
[http://dx.doi.org/10.1146/annurev.med.59.053006.104707] [PMID: 19630570]
[11]
Iorio, M.V.; Croce, C.M. microRNA involvement in human cancer. Carcinogenesis, 2012, 33(6), 1126-1133.
[http://dx.doi.org/10.1093/carcin/bgs140] [PMID: 22491715]
[12]
Wiggins, J.F. Development of a lung cancer therapeutic based on the tumor suppressor MicroRNA-34. Cancer Res., 2010, 70(14), 5923-5930.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-0655]
[13]
Wang, D.; Qiu, C.; Zhang, H.; Wang, J.; Cui, Q.; Yin, Y. Human microRNA oncogenes and tumor suppressors show significantly different biological patterns: From functions to targets. PLoS One, 2010, 5(9), e13067.
[http://dx.doi.org/10.1371/journal.pone.0013067] [PMID: 20927335]
[14]
Wang, Y.; Zeng, J.; Pan, J.; Geng, X.; Li, L.; Wu, J.; Song, P.; Wang, Y.; Liu, J.; Wang, L. MiR-320a inhibits gastric carcinoma by targeting activity in the FoxM1-P27KIP1axis. Oncotarget, 2016, 7(20), 29275-29286.
[15]
Wang, Y. MiR-320b is down-regulated in psoriasis and modulates keratinocyte proliferation by targeting akT3. Inflammation, 2018, 41(6), 2160-2170.
[16]
Lv, Q.L.; Du, H.; Liu, Y.L.; Huang, Y.T.; Wang, G.H.; Zhang, X.; Chen, S.H.; Zhou, H.H. Low expression of microRNA-320b correlates with tumorigenesis and unfavorable prognosis in glioma. Oncol. Rep., 2017, 38(2), 959-966.
[http://dx.doi.org/10.3892/or.2017.5762] [PMID: 28656255]
[17]
Zhang, L.; Yao, Z.; Liu, M.; Liu, Y. MiR-320b negatively regulates ovariectomy-induced osteoporosis in rats by decreasing RUNX2. Panminerva Med., 2019. Online ahead of print.
[http://dx.doi.org/10.23736/S0031-0808.19.03695-4] [PMID: 31355604]
[18]
Huang, C.; Qiu, Z.; Wang, L.; Peng, Z.; Jia, Z.; Logsdon, C.D.; Le, X.; Wei, D.; Huang, S.; Xie, K. A novel FoxM1-caveolin signaling pathway promotes pancreatic cancer invasion and metastasis. Cancer Res., 2012, 72(3), 655-665.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-3102] [PMID: 22194465]
[19]
Kong, X.; Li, L.; Li, Z.; Le, X.; Huang, C.; Jia, Z.; Cui, J.; Huang, S.; Wang, L.; Xie, K. Dysregulated expression of FOXM1 isoforms drives progression of pancreatic cancer. Cancer Res., 2013, 73(13), 3987-3996.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-3859] [PMID: 23598278]
[20]
Tang, X.S.X.; Nianfei, W.; Wanren, P.; Zhendong, C. MicroRNA-215-3p suppresses the growth, migration, and invasion of colorectal cancer by targeting FOXM1. Technol. Cancer Res. Treat., 2019, 18, 153303381987477.
[21]
Cui, J. FOXM1 promotes the warburg effect and pancreatic cancer progression via transactivation of LDHA expression. Clin. Cancer Res., 2014, 20(10), 2595-2606.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-2407]
[22]
Krain, L.S. Why is pancreatic cancer incidence up; stomach cancer down? Geriatrics, 1973, 28(4), 140-145.
[PMID: 4700067]
[23]
Rheinheimer, B. Abstract B13: Epigenetic silencing alters the SLIT2/ROBO1/miR-218-1 signaling axis in pancreatic cancer. Cancer Res., 2013, 73(13)(Suppl.), B13-B13.
[24]
Yuan, P. KRAS-NFĸB-YY1-miR-489 signaling axis controls pancreatic cancer metastasis. Cancer Res., 2017, 77(1), 100-111.
[PMID: 27793842]
[25]
Ling, J.W.F.; Liu, C. FOXO1-regulated lncRNA LINC01197 inhibits pancreatic adenocarcinoma cell proliferation by restraining Wnt/β-catenin signaling. J. Exp. Clin. Cancer Res., 2019, (38), 1.
[26]
Yan, H.; Li, Q.; Wu, J.; Hu, W.; Jiang, J.; Shi, L.; Yang, X.; Zhu, D.; Ji, M.; Wu, C. MiR-629 promotes human pancreatic cancer progression by targeting FOXO3. Cell Death Dis., 2017, 8(10), e3154.
[http://dx.doi.org/10.1038/cddis.2017.525] [PMID: 29072689]
[27]
Zhou, Y.Z.L.; Yinglu, D.; Peng, Z.; Jinqing, W. MicroRNA-340 suppresses pancreatic cancer growth by targeting BICD2,2019. Pancreatology, 2019, S1424-3903(19)30556-3..
[28]
Halasi, M.; Gartel, A.L. FOX(M1) news--it is cancer. Mol. Cancer Ther., 2013, 12(3), 245-254.
[http://dx.doi.org/10.1158/1535-7163.MCT-12-0712] [PMID: 23443798]
[29]
Gentles, A.J.; Newman, A.M.; Liu, C.L.; Bratman, S.V.; Feng, W.; Kim, D.; Nair, V.S.; Xu, Y.; Khuong, A.; Hoang, C.D.; Diehn, M.; West, R.B.; Plevritis, S.K.; Alizadeh, A.A. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat. Med., 2015, 21(8), 938-945.
[http://dx.doi.org/10.1038/nm.3909] [PMID: 26193342]
[30]
Bao, B.; Wang, Z.; Ali, S.; Kong, D.; Banerjee, S.; Ahmad, A.; Li, Y.; Azmi, A.S.; Miele, L.; Sarkar, F.H. Over-expression of FoxM1 leads to epithelial-mesenchymal transition and cancer stem cell phenotype in pancreatic cancer cells. J. Cell. Biochem., 2011, 112(9), 2296-2306.
[http://dx.doi.org/10.1002/jcb.23150] [PMID: 21503965]
[31]
Xia, J.T.; Wang, H.; Liang, L.J.; Peng, B.G.; Wu, Z.F.; Chen, L.Z.; Xue, L.; Li, Z.; Li, W. Overexpression of FOXM1 is associated with poor prognosis and clinicopathologic stage of pancreatic ductal adenocarcinoma. Pancreas, 2012, 41(4), 629-635.
[http://dx.doi.org/10.1097/MPA.0b013e31823bcef2] [PMID: 22249132]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy