Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Tumor Biology
Published in: Tumor Biology 3/2015

01-03-2015 | Research Article

MicroRNA-93 suppress colorectal cancer development via Wnt/β-catenin pathway downregulating

Authors: Qingchao Tang, Zhaoxia Zou, Chendan Zou, Qian Zhang, Rui Huang, Xu Guan, Qiang Li, Zhongjing Han, Dayong Wang, Huiyan Wei, Xu Gao, Xishan Wang

Published in: Tumor Biology | Issue 3/2015

Login to get access

Abstract

MicroRNA-93 (miR-93) is involved in several carcinoma progressions. It has been reported that miR-93 acts as a promoter or suppressor in different tumors. However, till now, the role of miR-93 in colon cancer is unclear. Herein, we have found that expression of miR-93 was lower in human colon cancer tissue and colorectal carcinoma cell lines compared with normal colon mucosa. Forced expression of miR-93 in colon cancer cells inhibits colon cancer invasion, migration, and proliferation. Furthermore, miR-93 may downregulate the Wnt/β-catenin pathway, which was confirmed by measuring the expression level of the β-catenin, axin, c-Myc, and cyclin-D1 in this pathway. Mothers against decapentaplegic homolog 7 (Smad7), as an essential molecular protein for nuclear accumulation of β-catenin in the canonical Wnt signaling pathway, is predicted as a putative target gene of miR-93 by the silico method and demonstrated that it may be suppressed by targeting its 3′UTR. These findings showed that miR-93 suppresses colorectal cancer development via downregulating Wnt/β-catenin, at least in part, by targeting Smad7. This study revealed that miR-93 is an important negative regulator in colon cancer and suggested that miR-93 may serve as a novel therapeutic agent that offers benefits for colon cancer treatment.
Appendix
Available only for authorised users
Literature
1.
Schoen RE, Pinsky PF, Weissfeld JL, Yokochi LA, Church T, Laiyemo AO, et al. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med. 2012;366:2345–57.CrossRefPubMedPubMedCentral
2.
Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007;57:43–66.CrossRefPubMed
3.
Dean M. Cancer as a complex developmental disorder–nineteenth Cornelius P. Rhoads Memorial Award Lecture. Cancer Res. 1998;58:5633–6.PubMed
4.
5.
Liang HH, Wei PL, Hung CS, Wu CT, Wang W, Huang MT, et al. MicroRNA-200a/b influenced the therapeutic effects of curcumin in hepatocellular carcinoma (HCC) cells. Tumour Biol. 2013;34:3209–18.CrossRefPubMed
6.
7.
Bienertova-Vasku J, Mazanek P, Hezova R, Curdova A, Nekvindova J, Kren L, et al. Extension of microRNA expression pattern associated with high-risk neuroblastoma. Tumour Biol. 2013;34:2315–9.CrossRefPubMed
8.
9.
Petrocca F, Vecchione A, Croce CM. Emerging role of miR-106b-25/miR-17-92 clusters in the control of transforming growth factor beta signaling. Cancer Res. 2008;68:8191–4.CrossRefPubMed
10.
Yang IP, Tsai HL, Hou MF, Chen KC, Tsai PC, Huang SW, et al. MicroRNA-93 inhibits tumor growth and early relapse of human colorectal cancer by affecting genes involved in the cell cycle. Carcinogenesis. 2012;33:1522–30.CrossRefPubMed
11.
12.
Fang L, Deng Z, Shatseva T, Yang J, Peng C, Du WW, et al. MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-beta8. Oncogenesis. 2011;30:806–21.CrossRef
13.
Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, et al. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997;275:1787–90.CrossRefPubMed
14.
Hu X, Li L, Shang M, Zhou J, Song X, Lu X, et al. Association between microRNA genetic variants and susceptibility to colorectal cancer in Chinese population. Tumour Biol. 2014;35:2151–6.CrossRefPubMed
15.
Satoh S, Daigo Y, Furukawa Y, Kato T, Miwa N, Nishiwaki T, et al. AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1. Nat Genet. 2000;24:245–50.CrossRefPubMed
16.
Barker N, Clevers H. Mining the Wnt pathway for cancer therapeutics. Nat Rev Drug Discov. 2006;5:997–1014.CrossRefPubMed
17.
18.
Brabletz T, Jung A, Hermann K, Gunther K, Hohenberger W, Kirchner T. Nuclear overexpression of the oncoprotein beta-catenin in colorectal cancer is localized predominantly at the invasion front. Pathol Res Pract. 1998;194:701–4.CrossRefPubMed
19.
Edlund S, Lee SY, Grimsby S, Zhang S, Aspenstrom P, Heldin CH, et al. Interaction between Smad7 and beta-catenin: importance for transforming growth factor beta-induced apoptosis. Mol Cell Biol. 2005;25:1475–88.CrossRefPubMedPubMedCentral
20.
Li Q, Zou C, Zou C, Han Z, Xiao H, Wei H, et al. MicroRNA-25 functions as a potential tumor suppressor in colon cancer by targeting Smad7. Cancer Lett. 2013;335:168–74.CrossRefPubMed
21.
Xiao ZG, Deng ZS, Zhang YD, Zhang Y, Huang ZC. Clinical significance of microRNA-93 downregulation in human colon cancer. Eur J Gastroenterol Hepatol. 2013;25:296–301.CrossRefPubMed
22.
Mandel K, Seidl D, Rades D, Lehnert H, Gieseler F, Hass R, et al. Characterization of spontaneous and TGF-beta-induced cell motility of primary human normal and neoplastic mammary cells in vitro using novel real-time technology. PLoS One. 2013;8:e56591.CrossRefPubMedPubMedCentral
23.
Wang Y, Tang Q, Li M, Jiang S, Wang X. MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA. Biochem Biophys Res Commun. 2014;444:199–204.CrossRefPubMed
24.
25.
Slattery ML, Herrick J, Curtin K, Samowitz W, Wolff RK, Caan BJ, et al. Increased risk of colon cancer associated with a genetic polymorphism of SMAD7. Cancer Res. 2010;70:1479–85.CrossRefPubMedPubMedCentral
26.
Scholer-Dahirel A, McLaughlin ME. Determinants of Wnt/beta-catenin pathway dependency in colorectal cancer. Cell Cycle. 2012;11:9–10.CrossRefPubMed
27.
Tenbaum SP, Ordonez-Moran P, Puig I, Chicote I, Arques O, Landolfi S, et al. β-catenin confers resistance to PI3K and AKT inhibitors and subverts FOXO3a to promote metastasis in colon cancer. Nat Med. 2012;18:892–901.CrossRefPubMed
28.
Guo Q, Shen S, Liao M, Lian P, Wang X. NGX6 inhibits cell invasion and adhesion through suppression of Wnt/beta-catenin signal pathway in colon cancer. Acta Biochim Biophys Sin (Shanghai). 2010;42:450–6.CrossRef
29.
Sivadas VP, Kannan S. The microRNA networks of TGFbeta signaling in cancer. Tumour Biol. 2014;35:2857–69.CrossRefPubMed
Metadata
Title
MicroRNA-93 suppress colorectal cancer development via Wnt/β-catenin pathway downregulating
Authors
Qingchao Tang
Zhaoxia Zou
Chendan Zou
Qian Zhang
Rui Huang
Xu Guan
Qiang Li
Zhongjing Han
Dayong Wang
Huiyan Wei
Xu Gao
Xishan Wang
Publication date
01-03-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 3/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2771-6

Other articles of this Issue 3/2015

Tumor Biology 3/2015 Go to the issue

Review

Molecular mechanism underlying the tumor-promoting functions of carcinoma-associated fibroblasts

Research Article

Combinatorial immunotherapy of sorafenib and blockade of programmed death-ligand 1 induces effective natural killer cell responses against hepatocellular carcinoma

Research Article

miRNA-646 suppresses osteosarcoma cell metastasis by downregulating fibroblast growth factor 2 (FGF2)

Research Article

DNA repair gene polymorphisms and clinical outcome of patients with primary small cell carcinoma of the esophagus

Research Article

Predictive impact of genetic polymorphisms in DNA repair genes on susceptibility and therapeutic outcomes to colorectal cancer patients

Research Article

Methylation of miR124a-1, miR124a-2, and miR124a-3 in Hodgkin lymphoma
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits