Abstract
Evidence has shown that microRNAs (miRNAs) participate in the progression of CRC. Previous studies have indicated that miR-214-3p is abnormally expressed in various malignant tumors. However, the biological function it plays in CRC and the potential mechanism are unclear. Here, we demonstrated that miR-214-3p was obviously downregulated in CRC. Moreover, we found a strong correlation between the miR-214-3p level and tumor size and lymphatic metastasis. Furthermore, when miR-214-3p was decreased by an Lv-miR-214-3p inhibitor, the proliferation and migration of SW480 and HCT116 cells were significantly increased. As expected, the ability of proliferation and migration was significantly suppressed when miR-214-3p was overexpressed in DLD1 cells. According to the dual-luciferase reporter results, PLAGL2 was found to be a direct downstream molecule of miR-214-3p. Chromatin immunoprecipitation (CHIP) confirmed that MYH9, a well-known cytoskeleton molecule in CRC, was a direct targeting gene of PLAGL2. Silencing PLAGL2 or MYH9 could reverse the effect of a miR-214-3p inhibitor on CRC cells. In summary, our studies proved that low expression of miR-214-3p and overexpression of downstream PLAGL2 in CRC indicated a poor prognosis. MiR-214-3p suppressed the malignant behaviors of colorectal cancer by regulating the PLAGL2/MYH9 axis. MiR-214-3p might be a novel therapeutic target or prognostic marker for CRC.
Highlights
Colorectal cancer (CRC), the third most common cancer in the world, is a great challenge facing mankind [1]
We found that the miR214-3p/PLAGL2/MYH9 axis has a significant effect on proliferation and metastasis in CRC
MiR-214-3p was downregulated in CRC, and low expression of miR214-3p was significantly associated with tumor size and lymphatic metastasis in CRC
Summary
Colorectal cancer (CRC), the third most common cancer in the world, is a great challenge facing mankind [1]. The past decade has witnessed a significant increase in the incidence and mortality of CRC and a trend of occurrence in younger patients [2]. Improvements in clinical diagnosis and comprehensive therapy have partly prolonged survival, the incidence and mortality of colorectal cancer are still high. The etiology and pathogenesis of colorectal cancer are not fully understood, but environmental, ethnic, economic www.aging-us.com and genetic factors play an important role in the progression of CRC. The high mortality and recurrence rates and the poor prognosis of colorectal cancer seriously threaten human safety and quality of life. Increasing evidence has shown that microRNAs play a critical role in the pathophysiological processes of different cancers. MiR-328-3p promotes stemness and migration in ovarian cancer by targeting DDB2 [5]. MiR-204-5p inhibits metastasis in breast cancer by regulating PI3K/Akt signaling [6]
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