MicroRNA‑133b inhibits connective tissue growth factor in colorectal cancer and correlates with the clinical stage of the disease

Guo,Yihang; Li,Xiaorong; Lin,Changwei; Zhang,Yi; Hu,Gui; Zhou,Jianyu; Du,Juan; Gao,Kai; Gan,Yi; Deng,Hao

doi:10.3892/mmr.2014.3075

MicroRNA‑133b inhibits connective tissue growth factor in colorectal cancer and correlates with the clinical stage of the disease

Authors:
- Yihang Guo
- Xiaorong Li
- Changwei Lin
- Yi Zhang
- Gui Hu
- Jianyu Zhou
- Juan Du
- Kai Gao
- Yi Gan
- Hao Deng
View Affiliations

Affiliations: Department of General Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China, Department of General Surgery, The Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China, Center for Experimental Medicine, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
Published online on: December 10, 2014 https://doi.org/10.3892/mmr.2014.3075
Pages: 2805-2812

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Accumulating evidence indicates that dysregulation of microRNA‑133b (miR‑133b) is an important step in the development of certain types of human cancer and contributes to tumorigenesis. Altered expression of miR‑133b has been reported in colon carcinoma, but its association with clinical stage in colorectal cancer (CRC) has remained elusive. Connective tissue growth factor (CTGF), a potentially promising candidate gene for interaction with miR‑133b, was screened using microarray analysis. The expression of miR‑133b and CTGF was evaluated using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The regulatory effects of miR‑133b on CTGF were evaluated using a dual‑luciferase reporter assay. CTGF was identified as a functional target of miR‑133b. The results demonstrated low expression of miR‑133b in CRC specimens with poor cell differentiation (P=0.011), lymph node metastasis (P=0.037) and advanced clinical stages (stage III or IV vs. I or II; P=0.036). Furthermore, there was a significant association between a high level of expression of CTGF mRNA and an advanced clinical stage (stage III or IV vs. I or II; P=0.015) and lymph node metastasis (P=0.034). CTGF expression was negatively regulated by miR‑133b in the human colorectum, suggesting that miR‑133b and CTGF may be candidate therapeutic targets in colorectal cancer.

View Figures

View References

1	Rossi S, Di Narzo AF, Mestdagh P, et al: microRNAs in colon cancer: a roadmap for discovery. FEBS Lett. 586:3000–3007. 2012. View Article : Google Scholar : PubMed/NCBI
2	Gansler T, Ganz PA, Grant M, et al: Sixty years of CA: a cancer journal for clinicians. CA Cancer J Clin. 60:345–350. 2010. View Article : Google Scholar : PubMed/NCBI
3	Lamy P, Andersen CL, Dyrskjøt L, Tørring N, Ørntoft T and Wiuf C: Are microRNAs located in genomic regions associated with cancer? Br J Cancer. 95:1415–1418. 2006. View Article : Google Scholar : PubMed/NCBI
4	Duisters RF, Tijsen AJ, Schroen B, et al: miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling. Circ Res. 104:170–178. 6p2009. View Article : Google Scholar
5	Wen D, Li S, Ji F, et al: miR-133b acts as a tumor suppressor and negatively regulates FGFR1 in gastric cancer. Tumour Biol. 34:793–803. 2013. View Article : Google Scholar : PubMed/NCBI
6	Hu G, Chen D, Li X, Yang K, Wang H and Wu W: miR-133b regulates the MET proto-oncogene and inhibits the growth of colorectal cancer cells in vitro and in vivo. Cancer Biol Ther. 10:190–197. 2010. View Article : Google Scholar : PubMed/NCBI
7	Chen CC and Lau LF: Functions and mechanisms of action of CCN matricellular proteins. Int J Biochem Cell Biol. 41:771–783. 2009. View Article : Google Scholar :
8	Chu CY, Chang CC, Prakash E and Kuo ML: Connective tissue growth factor (CTGF) and cancer progression. J Biomed Sci. 15:675–685. 2008. View Article : Google Scholar : PubMed/NCBI
9	Garcia P, Leal P, Ili C, Brebi P, Alvarez H and Roa JC: Inhibition of connective tissue growth factor (CTGF/CCN2) in gallbladder cancer cells leads to decreased growth in vitro. Int J Exp Pathol. 94:195–202. 2013.PubMed/NCBI
10	Kang Y, Siegel PM, Shu W, et al: A multigenic program mediating breast cancer metastasis to bone. Cancer Cell. 3:537–549. 2003. View Article : Google Scholar : PubMed/NCBI
11	Deng YZ, Chen PP, Wang Y, et al: Connective tissue growth factor is overexpressed in esophageal squamous cell carcinoma and promotes tumorigenicity through beta-catenin-T-cell factor/Lef signaling. J Biol Chem. 282:36571–36581. 2007. View Article : Google Scholar : PubMed/NCBI
12	Wenger C, Ellenrieder V, Alber B, et al: Expression and differential regulation of connective tissue growth factor in pancreatic cancer cells. Oncogene. 18:1073–1080. 1999. View Article : Google Scholar : PubMed/NCBI
13	Kubo M, Kikuchi K, Nashiro K, et al: Expression of fibrogenic cytokines in desmoplastic malignant melanoma. Br J Dermatol. 139:192–197. 1998. View Article : Google Scholar : PubMed/NCBI
14	Shakunaga T, Ozaki T, Ohara N, et al: Expression of connective tissue growth factor in cartilaginous tumors. Cancer. 89:1466–1473. 2000. View Article : Google Scholar : PubMed/NCBI
15	Lee HK, Bier A, Cazacu S, et al: MicroRNA-145 is downregulated in glial tumors and regulates glioma cell migration by targeting connective tissue growth factor. PLoS One. 8:e546522013. View Article : Google Scholar : PubMed/NCBI
16	Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL and Trotti A: AJCC Cancer Staging Manual. 7th edition. Springer; New York, NY: 2010
17	Xiang KM and Li XR: MiR-133b acts as a tumor suppressor and negatively regulates TBPL1 in colorectal cancer cells. Asian Pac J Cancer Prev. 15:3767–3772. 2014. View Article : Google Scholar : PubMed/NCBI
18	Lin CW, Li XR, Zhang Y, et al: TAp63 suppress metastasis via miR-133b in colon cancer cells. Br J Cancer. 110:2310–2320. 2014. View Article : Google Scholar : PubMed/NCBI
19	Wen D, Li S, Ji F, Cao H, Jiang W, Zhu J and Fang X: Mir-133b acts as a tumor suppressor and negatively regulates FGFR1 in gastric cancer. Tumour Biol. 34:793–803. 2013. View Article : Google Scholar : PubMed/NCBI
20	Crawford M, Batte K, Yu L, Wu X, Nuovo GJ, Marsh CB, Otterson GA and Nana-Sinkam SP: MicroRNA-133b targets pro-survival molecules MCL-1 and BCL2L2 in lung cancer. Biochem Biophys Res Commun. 388:483–489. 2009. View Article : Google Scholar : PubMed/NCBI
21	Ichimi T, Enokida H, Okuno Y, Kunimoto R, Chiyomaru T, Kawamoto K, Kawahara K, Toki K, Kawakami K, Nishiyama K, et al: Identification of novel microRNA targets based on microRNA signatures in bladder cancer. Int J Cancer. 125:345–352. 2009. View Article : Google Scholar : PubMed/NCBI
22	Duisters RF, Tijsen AJ, Schroen B, et al: miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling. Circ Res. 104:170–178. 2009. View Article : Google Scholar
23	Hofmeister V, Schrama D and Becker JC: Anti-cancer therapies targeting the tumor stroma. Cancer Immunol Immunother. 57:1–17. 2008. View Article : Google Scholar
24	Wendt MK, Smith JA and Schiemann WP: Transforming growth factor-β-induced epithelial-mesenchymal transition facilitates epidermal growth factor-dependent breast cancer progression. Oncogene. 29:6485–6498. 2010. View Article : Google Scholar : PubMed/NCBI
25	Wang B, Herman-Edelstein M, Koh P, Burns W, Jandeleit-Dahm K, Watson A, Saleem M, Goodall GJ, Twigg SM, Cooper ME and Kantharidis P: E-cadherin expression is regulated by miR-192/215 by a mechanism that is independent of the profibrotic effects of transforming growth factor-beta. Diabetes. 59:1794–1802. 2010. View Article : Google Scholar : PubMed/NCBI
26	Secker GA, Shortt AJ, Sampson E, Schwarz QP, Schultz GS and Daniels JT: TGFbeta stimulated re-epithelialisation is regulated by CTGF and Ras/MEK/ERK signalling. Exp Cell Res. 314:131–142. 2008. View Article : Google Scholar
27	Babic AM, Chen CC and Lau LF: Fisp12/mouse connective tissue growth factor mediates endothelial cell adhesion and migration through integrin alphavbeta3, promotes endothelial cell survival, and induces angiogenesis in vivo. Mol Cell Bio. 19:2958–2966. 1999.
28	Lau LF and Lam SC: The CCN family of angiogenic regulators: the integrin connection. Exp Cell Res. 248:44–57. 1999. View Article : Google Scholar : PubMed/NCBI
29	Dornhöfer N, Spong S, Bennewith K, Salim A, Klaus S, Kambham N, Wong C, Kaper F, Sutphin P, Nacamuli R, et al: Connective tissue growth factor-specific monoclonal antibody therapy inhibits pancreatic tumor growth and metastasis. Cancer Res. 66:5816–5827. 2006. View Article : Google Scholar : PubMed/NCBI