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Downregulation of microRNA-15a suppresses the proliferation and invasion of renal
cell carcinoma via direct targeting of eIF4E
#MMPMID28849086
Li G
; Chong T
; Xiang X
; Yang J
; Li H
Oncol Rep
2017[Oct]; 38
(4
): 1995-2002
PMID28849086
show ga
The downregulation of microRNA-15a has been reported in several human tumors.
However, its expression and functional importance in renal cell carcinoma (RCC)
remain unknown. The aim of the present study was to investigate its expression,
biological functions and underlying mechanisms in RCC tumorigenesis. The
expression levels of miR-15a were examined by qRT-PCR in 40 RCC specimens and
adjacent?paired normal tissues. Cell Counting Kit-8 (CCK-8), colony formation,
flow cytometry and Transwell assays were used to explore the potential influence
of miR-15a transfection on RCC cell proliferation, the cell cycle, cell
apoptosis, and cell invasion. Luciferase reporter assays were performed to
confirm the potential target of miR-15a, in combination with qRT-PCR, western
blotting and immunohistochemical assays. We found that miR-15a was significantly
downregulated in most RCC specimens compared with adjacent normal
tissues (P<0.01). Overexpression of miR-15a inhibited cellular growth, suppressed
invasion and arrested cells at the G1/G0 phase, and induced cell apoptosis in RCC
cells. Luciferase assays revealed that miR-15a directly targeted the binding site
of the 3'-untranslated region (3'-UTR) of eIF4E, and inhibited its expression at
both mRNA and protein levels. eIF4E expression was negatively associated with
miR-15a expression in RCC tissues. eIF4E overexpression treatment partially
abrogated the inhibitory effect of miR-15a on cell proliferation and invasion, as
well as inactivated P13K/AKT/mTOR signaling in RCC cells. In conclusion, the
present study indicated that miR-15a downregulation was associated with cell
proliferation and invasion by directly targeting eIF4E during RCC progression.
Thus, it may serve as a potential tumor suppressor and therapeutic target for the
treatment of RCC.
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