Abstract
Objective: To explore the biological function and mechanism of miR-96-5p in gastric cancer.Methods: The expression of differently expressed microRNAs (DEMs) related to gastric adenocarcinoma (GAC) prognosis was identified in GAC tumor samples and adjacent normal samples by qRT-PCR. A target gene miR-96-5p was selected using TargetScan, miRTarBase, miRDB databases. The combination of miR-96-5p and ZDHHC5 was verified by luciferase receptor assay. To further study the function and mechanism of miR-96-5p, we treated MGC-803 cells with miR-96-5p inhibitor and si-ZDHHC5, then detected cell viability, apoptosis, migration and invasion ability, as well as the expression of ZDHHC5, Bcl-2, Bax, cleaved caspase-3, cleaved caspase-9, and COX-2 by Western blot.Results: Compared with adjacent normal samples, the levels of miR-96-5p, miR-222-5p, and miR-652-5p were remarkably increased, while miR-125-5p, miR-145-3p, and miR-379-3p were significantly reduced in GAC tumor samples (P<0.01), which were consistent with bioinformatics analysis. Furthermore, ZDHHC5 was defined as a direct target gene of miR-96-5p. miR-96-5p silence significantly reduced cell viability, increased cell apoptosis, and suppressed cell migration and invasion, as well as inhibited the expression of Bcl-2 and COX-2 and promoted Bax, cleaved caspase-3 and cleaved caspase-9 level in MGC-803 cells (P<0.01). Notably, ZDHHC5 silence reversed the inhibiting effects of miR-96-5p on MGC-803 cells growth and metastasisConclusion: Our findings identified six microRNAs (miRNAs; miR-96-5p, miR-222-5p, miR-652-5p, miR-125-5p, miR-145-3p, and miR-379-3p) related to GAC prognosis, and suggested that down-regulated miR-96-5p might inhibit tumor cell growth and metastasis via increasing ZDHHC5 expression enhance MGC-803 cell apoptosis, as well as decrease MGC-803 cell metastasis.
Highlights
Gastric adenocarcinoma (GAC) is the most common malignant tumor originating in the stomach, with approximately 951000 diagnosed cases and 723000 deaths in 2012 [1,2]
Based on these 299 differently expressed microRNA (DEM), the relationship between patient overall survival (OS) and miRNA expression was evaluated, and the results showed that 35 DEMs were significantly related to the prognosis of GAC patients (P
RT-quantitative polymerase chain reaction (qPCR) showed that compared with adjacent normal samples, the levels of miR-96-5p, miR-222-5p, and miR-652-5p were remarkably increased, while miR-125-5p, miR-145-3p, and miR-379-3p levels were obviously reduced in GAC tumor samples (P
Summary
Gastric adenocarcinoma (GAC) is the most common malignant tumor originating in the stomach, with approximately 951000 diagnosed cases and 723000 deaths in 2012 [1,2]. The common and effective treatment method is to combine surgery with adjuvant radiotherapy or chemotherapy to improve the 5-year survival rate of GAC [3]. Due to atypical symptoms of early GAC, most patients with proximal or distal metastases find delayed diagnosis, which leads to poor treatment and prognosis [4]. It is well known that a major challenge of GAC treatment is poor prognosis, and environmental exposures and genetic mutations have been identified to be associated with this outcome [5]. A large body of evidence indicates that the poor prognosis of GAC is significantly associated with many molecular biomarkers such as microRNA (miRNA) [6,7]. It has been revealed that a large number of miRNAs are involved in various biological functions such as cell differentiation, apoptosis, migration, invasion, and proliferation in human
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