MicroRNA-96 promotes the proliferation of colorectal cancer cells and targets tumor protein p53 inducible nuclear protein 1, forkhead box protein O1 (FOXO1) and FOXO3a

Gao,Feng; Wang,Wenhui

doi:10.3892/mmr.2014.2854

February-2015 Volume 11 Issue 2

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

February-2015 Volume 11 Issue 2

Full Size Image

Article

MicroRNA-96 promotes the proliferation of colorectal cancer cells and targets tumor protein p53 inducible nuclear protein 1, forkhead box protein O1 (FOXO1) and FOXO3a

Authors:
- Feng Gao
- Wenhui Wang
View Affiliations / Copyright

Affiliations: Department of Anorectal Surgery, The People's Hospital of Weifang, Weifang, Shandong 261041, P.R. China, Department of Oncology, The People's Hospital of Weifang, Weifang, Shandong 261041, P.R. China
Pages: 1200-1206
|
Published online on: November 4, 2014

https://doi.org/10.3892/mmr.2014.2854
Expand metrics +

Abstract

MicroRNAs (miRNAs) are a conserved class of small, endogenous, non protein-coding RNA molecules that are capable of regulating gene expression at post-transcriptional levels and are involved in diverse cellular processes, including cancer pathogenesis. It has previously been reported that miRNA-96 (miR-96) is overexpressed in human colorectal cancer (CRC). However, the underlying mechanism of miR-96 regulation in CRC remains to be elucidated. In the present study, miR-96 was confirmed to be upregulated in CRC tissues by reverse transcription quantitative polymerase chain reaction. MTT assay, colony formation assay and cell cycle analysis revealed that miR-96 overexpression led to increased tumor cell viability, colony formation ability and cell cycle progression. By contrast, inhibition of miR-96 resulted in the suppression of cell proliferation. It was also demonstrated that miR-96 reduced the messenger RNA and protein expression levels of tumor protein p53 inducible nuclear protein 1 (TP53INP1), forkhead box protein O1 (FOXO1) and FOXO3a, which are closely associated with cell proliferation. A luciferase reporter assay indicated that miR-96 inhibited luciferase intensity controlled by the 3'UTRs of TP53INP1, FOXO1 and FOXO3a. In conclusion, the results of the present study demonstrated that miR-96 contributed to CRC cell growth and that TP53INP1, FOXO1 and FOXO3a were direct targets of miR-96, suggesting that miR-96 may have the potential to be used in the development of miRNA‑based therapies for CRC patients.

View Figures

View References

1	Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
2	Brennecke J, Stark A, Russell RB and Cohen SM: Principles of microRNA-target recognition. PLoS Biol. 3:e852005. View Article : Google Scholar : PubMed/NCBI
3	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
4	Calin GA, Sevignani C, Dumitru CD, et al: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 101:2999–3004. 2004. View Article : Google Scholar : PubMed/NCBI
5	Nassirpour R, Mehta PP and Yin MJ: miR-122 regulates tumorigenesis in hepatocellular carcinoma by targeting AKT3. PLoS One. 8:e796552013. View Article : Google Scholar : PubMed/NCBI
6	Gaziel-Sovran A, Segura MF, Di Micco R, et al: miR-30b/30d regulation of GalNAc transferases enhances invasion and immunosuppression during metastasis. Cancer Cell. 20:104–118. 2011. View Article : Google Scholar : PubMed/NCBI
7	Fearon ER: Molecular genetics of colorectal cancer. Annu Rev Pathol. 6:479–507. 2011. View Article : Google Scholar
8	Kanthan R, Senger JL and Kanthan SC: Molecular events in primary and metastatic colorectal carcinoma: a review. Patholog Res Int. 2012:5974972012.PubMed/NCBI
9	Kaemmerer E, Klaus C, Jeon MK and Gassler N: Molecular classification of colorectal carcinomas: The genotype-to-phenotype relation. World J Gastroenterol. 19:8163–8167. 2013. View Article : Google Scholar : PubMed/NCBI
10	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
11	Sarver AL, French AJ, Borralho PM, et al: Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states. BMC Cancer. 9:4012009. View Article : Google Scholar : PubMed/NCBI
12	Bandres E, Cubedo E, Agirre X, et al: Identification by real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. Mol Cancer. 5:292006. View Article : Google Scholar : PubMed/NCBI
13	Sarver AL, Li L and Subramanian S: MicroRNA miR-183 functions as an oncogene by targeting the transcription factor EGR1 and promoting tumor cell migration. Cancer Res. 70:9570–9580. 2010. View Article : Google Scholar : PubMed/NCBI
14	Khatri R and Subramanian S: MicroRNA-135b and its circuitry networks as potential therapeutic targets in colon cancer. Front Oncol. 3:2682013. View Article : Google Scholar : PubMed/NCBI
15	Cekaite L, Rantala JK, Bruun J, et al: MiR-9, -31, and -182 deregulation promote proliferation and tumor cell survival in colon cancer. Neoplasia. 14:868–879. 2012.PubMed/NCBI
16	Chen C, Ridzon DA, Broomer AJ, et al: Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 33:e1792005. View Article : Google Scholar : PubMed/NCBI
17	Haflidadottir BS, Larne O, Martin M, et al: Upregulation of miR-96 enhances cellular proliferation of prostate cancer cells through FOXO1. PLoS One. 8:e724002013. View Article : Google Scholar : PubMed/NCBI
18	Lin H, Dai T, Xiong H, et al: Unregulated miR-96 induces cell proliferation in human breast cancer by downregulating transcriptional factor FOXO3a. PLoS One. 5:e157972010. View Article : Google Scholar
19	Guttilla IK and White BA: Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells. J Biol Chem. 284:23204–23216. 2009. View Article : Google Scholar : PubMed/NCBI
20	Xu D, He X, Chang Y, et al: Inhibition of miR-96 expression reduces cell proliferation and clonogenicity of HepG2 hepatoma cells. Oncol Rep. 29:653–661. 2013.
21	Fendler A, Jung M, Stephan C, et al: The antiapoptotic function of miR-96 in prostate cancer by inhibition of FOXO1. PLoS One. 8:e808072013. View Article : Google Scholar : PubMed/NCBI
22	Yu S, Lu Z, Liu C, et al: miRNA-96 suppresses KRAS and functions as a tumor suppressor gene in pancreatic cancer. Cancer Res. 70:6015–6025. 2010. View Article : Google Scholar : PubMed/NCBI
23	Xu N, Zhang L, Meisgen F, et al: MicroRNA-125b down-regulates matrix metallopeptidase 13 and inhibits cutaneous squamous cell carcinoma cell proliferation, migration, and invasion. J Biol Chem. 287:29899–29908. 2012. View Article : Google Scholar : PubMed/NCBI
24	Jiang F, Liu T, He Y, et al: MiR-125b promotes proliferation and migration of type II endometrial carcinoma cells through targeting TP53INP1 tumor suppressor in vitro and in vivo. BMC Cancer. 11:4252011. View Article : Google Scholar : PubMed/NCBI
25	Zhang CM, Zhao J and Deng HY: MiR-155 promotes proliferation of human breast cancer MCF-7 cells through targeting tumor protein 53-induced nuclear protein 1. J Biomed Sci. 20:792013. View Article : Google Scholar : PubMed/NCBI
26	Jiang PH, Motoo Y, Garcia S, et al: Down-expression of tumor protein p53-induced nuclear protein 1 in human gastric cancer. World J Gastroenterol. 12:691–696. 2006.PubMed/NCBI
27	Shahbazi J, Lock R and Liu T: Tumor protein 53-induced nuclear protein 1 enhances p53 function and represses tumorigenesis. Front Genet. 4:802013. View Article : Google Scholar : PubMed/NCBI
28	Ito Y, Motoo Y, Yoshida H, et al: Decreased expression of tumor protein p53-induced nuclear protein 1 (TP53INP1) in breast carcinoma. Anticancer Res. 26:4391–4395. 2006.
29	Maiese K, Chong ZZ, Shang YC and Hou J: Clever cancer strategies with FoxO transcription factors. Cell Cycle. 7:3829–3839. 2008. View Article : Google Scholar : PubMed/NCBI
30	Guo JP, Tian W, Shu S, et al: IKBKE phosphorylation and inhibition of FOXO3a: a mechanism of IKBKE oncogenic function. PLoS One. 8:e636362013. View Article : Google Scholar : PubMed/NCBI