MicroRNA-93 inhibits tumor growth and early relapse of human colorectal cancer by affecting genes involved in the cell cycle

I. Ping Yang, Hsiang Lin Tsai, Ming Feng Hou, Ku Chung Chen, Pei Chien Tsai, Szu Wei Huang, Wen Wen Chou, Jaw Yuan Wang, Suh Hang Hank Juo

Research output: Contribution to journalArticle

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Abstract

Purpose: Colorectal cancer (CRC) is associated with high recurrence and mortality. Because deregulation of microRNAs is associated with CRC development and recurrence, the expression levels of microRNAs can be a simple and reliable biomarker to detect postoperative early relapse, thereby helping physicians to treat high-risk patients more efficiently. Experimental design: We used microRNA arrays and observed that microRNA-93 had substantially different expression levels in early (recurrence within 12 months after surgery) and non-early relapse CRC patients. The replication study, which included 35 early relapse and 42 non-early relapse subjects, further confirmed overexpression of microRNA-93 in non-early relapse samples. The in vitro and in vivo effects of microRNA-93 were investigated by examining cell proliferation, migration and invasion, as well as cell cycles, target-gene expression and xenograft in null mice. Results: Cellular studies showed that the overexpression of microRNA-93 inhibited colon cancer cell proliferation and migration but not invasion. The cell cycle studies also revealed that microRNA-93 caused an accumulation of the G2 population. However, microRNA-93 could not induce cell apoptosis or necrosis. Functional studies showed that microRNA-93 could suppress CCNB1 protein expression leading to cell cycle arrest in the G2 phase. Moreover, microRNA-93 repressed expression of ERBB2, p21 and VEGF, all of which are involved in cell proliferation. MicroRNA-93 also suppressed tumor growth in null mice. Conclusions: This study showed that microRNA-93 can inhibit tumorigenesis and reduce the recurrence of CRC; these findings may have potential clinical applications for predicting the recurrence of CRC.

Original languageEnglish
Pages (from-to)1522-1530
Number of pages9
JournalCarcinogenesis
Volume33
Issue number8
DOIs
Publication statusPublished - Aug 2012
Externally publishedYes

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Neoplasm Genes
MicroRNAs
Colorectal Neoplasms
Cell Cycle
Recurrence
Growth
Neoplasms
Cell Proliferation
Cell Movement
cdc Genes
G2 Phase
Cell Cycle Checkpoints
Heterografts
Colonic Neoplasms
Vascular Endothelial Growth Factor A
Carcinogenesis
Research Design
Necrosis
Biomarkers

ASJC Scopus subject areas

  • Cancer Research

Cite this

MicroRNA-93 inhibits tumor growth and early relapse of human colorectal cancer by affecting genes involved in the cell cycle. / Yang, I. Ping; Tsai, Hsiang Lin; Hou, Ming Feng; Chen, Ku Chung; Tsai, Pei Chien; Huang, Szu Wei; Chou, Wen Wen; Wang, Jaw Yuan; Juo, Suh Hang Hank.

In: Carcinogenesis, Vol. 33, No. 8, 08.2012, p. 1522-1530.

Research output: Contribution to journalArticle

Yang, I. Ping ; Tsai, Hsiang Lin ; Hou, Ming Feng ; Chen, Ku Chung ; Tsai, Pei Chien ; Huang, Szu Wei ; Chou, Wen Wen ; Wang, Jaw Yuan ; Juo, Suh Hang Hank. / MicroRNA-93 inhibits tumor growth and early relapse of human colorectal cancer by affecting genes involved in the cell cycle. In: Carcinogenesis. 2012 ; Vol. 33, No. 8. pp. 1522-1530.
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AU - Chou, Wen Wen

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N2 - Purpose: Colorectal cancer (CRC) is associated with high recurrence and mortality. Because deregulation of microRNAs is associated with CRC development and recurrence, the expression levels of microRNAs can be a simple and reliable biomarker to detect postoperative early relapse, thereby helping physicians to treat high-risk patients more efficiently. Experimental design: We used microRNA arrays and observed that microRNA-93 had substantially different expression levels in early (recurrence within 12 months after surgery) and non-early relapse CRC patients. The replication study, which included 35 early relapse and 42 non-early relapse subjects, further confirmed overexpression of microRNA-93 in non-early relapse samples. The in vitro and in vivo effects of microRNA-93 were investigated by examining cell proliferation, migration and invasion, as well as cell cycles, target-gene expression and xenograft in null mice. Results: Cellular studies showed that the overexpression of microRNA-93 inhibited colon cancer cell proliferation and migration but not invasion. The cell cycle studies also revealed that microRNA-93 caused an accumulation of the G2 population. However, microRNA-93 could not induce cell apoptosis or necrosis. Functional studies showed that microRNA-93 could suppress CCNB1 protein expression leading to cell cycle arrest in the G2 phase. Moreover, microRNA-93 repressed expression of ERBB2, p21 and VEGF, all of which are involved in cell proliferation. MicroRNA-93 also suppressed tumor growth in null mice. Conclusions: This study showed that microRNA-93 can inhibit tumorigenesis and reduce the recurrence of CRC; these findings may have potential clinical applications for predicting the recurrence of CRC.

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