Abstract
Functions and mechanisms of microRNA (miRNA) involved in colorectal cancer (CRC) metastasis are largely unknown. Here, a miRNA microarray analysis was performed in CRC primary tissues and metastatic hepatic tissues to disclose crucial miRNA involved in CRC metastasis. MiR-133b was decreased and negatively correlated with metastasis in CRC. Overexpression of miR-133b significantly suppressed metastasis of CRC in vitro and in vivo. HOXA9 was identified as a direct and functional target of miR-133b. In addition, HOXA9 was negatively correlated with miR-133b and promoted CRC malignant progress. Moreover, miR-133b decreased HOXA9 expression, and subsequently downregulated ZEB1 and upregulated E-cadherin expression. Intriguingly, lower miR-133b and higher HOXA9 expression significantly contributed to poorer outcomes in CRC patients. Multivariate analysis indicated that miR-133b was an independent and significant predictor of CRC patient overall survival. In conclusion, we newly determined that miR-133b targeted the HOXA9/ZEB1 pathway to promote tumor metastasis in CRC cells. This axis provided insights into the mechanism underlying miRNA regulation of CRC metastasis and a novel therapeutic target for CRC treatment.
Highlights
Colorectal cancer (CRC) is ordered as the second most prevalent cancer in women and the third most common cancer in men according to world health Organization [1]
To examine the expression of miR-133b in CRC, TCGA data was analyzed, which showed that miR-133b was significantly downregulated in CRC tissues compared to adjacent normal tissues (Figure 1B)
A decrease of miR-133b in the 10 CRC tissues with metastasis was remarked compared to primary tumors without metastasis (Figure 1C), which proposed that the down-regulation of miR-133b was strictly related to the progression of CRC metastasis
Summary
Colorectal cancer (CRC) is ordered as the second most prevalent cancer in women and the third most common cancer in men according to world health Organization [1]. Despite advances in therapeutic strategies, the clinical outcome and prognosis of CRC remains poor [2]. Tumor metastasis is a major cause of mortality in CRC [3]. Many cell growth and metastasis-related genes were found, the molecular mechanisms that suppress tumor cell growth, migration and invasion are largely unknown [4,5,6]. There has been an attention on the characterization of microRNAs in oncogenesis and tumor suppressing. These microRNAs have been described to take part in a diversity of cancers, especially in cell malignant progression [7,8,9,10]. MicroRNAs serve as important regulators of tumor development
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