Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide. Metastatic progression is a primary factor contributing to lethality of CRC patients. However, the molecular mechanisms forming early local invasion and distant metastatic colonies are still unclear and the present therapeutic approaches for CRC are unsatisfactory. Therefore, novel therapies targeting metastatic invasion that could prevent tumor spreading and recurrence are urgently needed. Our study showed that the decrease of miR-384 was found in 83.0% (83/100) CRC patients. And low-leveled expression of miR-384 was closely correlated with the invasive depth, lymph node and distant metastasis of CRC. Overexpression of miR-384 could inhibit the invasive and migrating abilities of CRC cells in vitro and the metastatic potential in vivo. Luciferase assays showed that miR-384 repressed the expression of Kirsten Ras (KRAS) and Cell division cycle 42 (CDC42) by directly targeting their 3’-untranslated regions. There is functional and mechanistic relationship between miRNA-384 and KRAS, CDC42 in the invasion and metastasis of CRC. And our findings suggest that miR-384could be a potent therapeutic target for CRC. Restoration of miR-384 expression might provide novel therapeutic approach to the reduction of CRC metastasis.
Highlights
Colorectal cancer (CRC) is the third most common cancer and one of the major causes of death globally [1]
Death from CRC is mainly due to metastatic progression, and the liver is the main organ of metastatic colonization in over 70% of patients [3, 4]. 50-60% of CRC patients can develop distant metastases and the 5-year survival rate will decrease to 5% in patients with distant metastases [5, 6]
We found that miR-384 was down-regulated in 83.0% (83/100) of CRC tissue samples (T) compared to their matched adjacent normal tissues (N)
Summary
Colorectal cancer (CRC) is the third most common cancer and one of the major causes of death globally [1]. Death from CRC is mainly due to metastatic progression, and the liver is the main organ of metastatic colonization in over 70% of patients [3, 4]. 50-60% of CRC patients can develop distant metastases and the 5-year survival rate will decrease to 5% in patients with distant metastases [5, 6]. Efforts to prevent metastasis and increase cure rates after surgery have focused on combined chemotherapy administration. Such therapy is unsatisfactory in reducing metastatic relapse. The high prevalence and lack of effective therapeutic targets of this disease demand a greater understanding of its biological progression [7]
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