Abstract
MicroRNAs are involved in tumor initiation and progression by regulating oncogenes and tumor suppressor genes. Here we found that miR-495 are lower in clinical ESCC tissues than in adjacent non-tumor tissues. Moreover, the lower miR-495 expression correlated with increased lymph node metastasis (LNM), invasion and TNM stage. miR-495 overexpression predicted a favorable outcome in ESCC patients. miR-495 targeted a site in the 3′-UTR of Akt1, and miR-495 levels correlated inversely with Akt1 protein levels in ESCC tissue samples. Overexpression of miR-495 suppressed cell proliferation, blocked G1/S phase transition, and decreased migration and invasion by two ESCC cell lines in vitro and in vivo. Restoration of Akt1 protein levels in miR-495-overexpressing ESCC cells attenuated the inhibitory effects of miR-495. In addition, miR-495 suppressed cell cycle transition and the EMT signaling pathway through targeting Akt1, thereby inhibiting ESCC cell proliferation, migration, and invasion. Our results suggest that miR-495 may act as a tumor suppressor by targeting Akt1 in ESCC.
Highlights
In East Asia, esophageal squamous cell carcinoma (ESCC) is the most predominant type of esophageal cancer [1]
The 2-ΔΔCt method revealed that miR-495 expression was downregulated in 85% (34/40) of the ESCC tissues compared to the paired non-tumor tissues patients using a 2-fold change criterion (Figure 1A)
Our results showed that lower miR-495 down-regulation was correlated with shorter progression-free survival (PFS) (P = 0.01) and overall survival (OS) (P = 0.03) times. (Figure 1D, 1E)
Summary
In East Asia, esophageal squamous cell carcinoma (ESCC) is the most predominant type of esophageal cancer [1]. Tumor proliferation and metastasis are two main factors responsible for ESCC progression [3]. The molecular mechanisms of tumor progression and metastasis remain unclear [1]. MicroRNAs (miRNAs) which are small, endogenous, non-coding RNAs, 20–24 nucleotides in length, play crucial roles in numerous cancerrelevant biological processes, such as differentiation, proliferation, migration and apoptosis [4, 5]. Overexpression of miR-495 inhibits tumor progression by inducing G0/G1 cell cycle arrest [9] and by suppressing angiogenesis and metastasis [12]. The specific function of miR-495 in ESCC progression still remains unclear. Bioinformatic analysis predicts that miR-495 might regulate the expression of Akt protein by directly targeting the 3′-UTR of its mRNA, which plays a central role in the PI3K/AKT pathway [14]
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