MicroRNA-135b regulates metastasis suppressor 1 expression and promotes migration and invasion in colorectal cancer.

Abstract

MicroRNAs (miRNAs, miRs) play important roles in pathogenesis and development of human diseases, including malignancy. Some may affect tumor progression through targeting tumor suppressor genes. MiR-135b has been shown to be upregulated in CRC. In this study, we evaluated the role of miR-135b in colorectal cancer (CRC) and its regulatory role for metastasis suppressor-1 (MTSS1) and its mechanisms. The levels of miR-135b and MTSS1 gene expression in 35 CRC and corresponding cancer-adjacent tissues, 27 colorectal adenoma, and 16 normal tissue samples were quantified using qRT-PCR and western blot analysis. The effect of miR-135b on MTSS1 expression was assessed by miR-135b mimics or inhibitor transfection to deregulate miR-135b expression. The direct interaction between them was verified by 3'-UTR dual-luciferase reporter assay. Furthermore, the roles of miR-135b in regulating CRC cells migration and invasion properties were analyzed with miR-135b mimics or inhibitor-transfected cells and silenced expression of MTSS1 in miR-135b inhibitor transfected cells. CRC tissues showed significantly upregulated miR-135b expression and reduced MTSS1 expression. High miR-135b levels were significantly associated with lymph node and distant metastasis. The miR-135b inhibitor decreased miR-135b expression and caused MTSS1 upregulation at the post-transcriptional level. However, overexpression of miR-135b caused MTSS1 protein downregulation. The 3'-UTR of MTSS1 harbored a binding site for miR-135b. Finally, miR-135b inhibitor-transfected cells exhibited markedly reduced cell migration and invasive abilities, and this effect could be reversed by MTSS1-siRNA. Our results demonstrated that miR-135b downregulated MTSS1 expression and contributed to CRC cell invasion, indicating its involvement in CRC progression.

• Authors: Weiyun Wu, Zhuang Wang, Pengchun Yang, Jingfang Yang, Jian Liang, Yuanhong Chen, Hao Wang, Guoli Wei, Shicai Ye, Yu Zhou
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 388 Issue 1-2 Pg. 249-59 (Mar 2014) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 24343340 (Publication Type: Journal Article)

Chemical References

• 3' Untranslated Regions
• MIRN135 microRNA, human
• MTSS1 protein, human
• MicroRNAs
• Microfilament Proteins
• Neoplasm Proteins
• RNA, Small Interfering

Topics

• 3' Untranslated Regions (genetics)
• Binding Sites (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation
• Colorectal Neoplasms (genetics, pathology)
• Female
• Gene Expression Regulation, Neoplastic
• HCT116 Cells
• Humans
• Lymphatic Metastasis (genetics, pathology)
• Male
• MicroRNAs (antagonists & inhibitors, biosynthesis, genetics)
• Microfilament Proteins (biosynthesis, genetics)
• Middle Aged
• Neoplasm Invasiveness (genetics, pathology)
• Neoplasm Proteins (biosynthesis, genetics)
• RNA Interference
• RNA, Small Interfering
• Wound Healing (drug effects, genetics)