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Abstract
BackgroundAnti-apoptotic protein Bcl-2 plays a substantial role in the carcinogenesis, whereas the regulation for Bcl-2 in gastric carcinoma (GC) is poorly understood. Specifically, a role of microRNA (miR)-383 in the control of Bcl-2 has not been shown in GC and thus addressed in the current study.MethodsWe investigated the levels of miR-383 and Bcl-2 in 50 GC specimens, and compared them with patients’ clinical characteristics. Bioinformatics analyses and luciferase-reporter assay were applied for analyzing the relationship between Bcl-2 and miR-383. An CCK assay was used to determine the survival of Fluorouracil-treated GC cells, and apoptosis of GC cells was assessed by flow cytometric FITC Annexin V apoptosis detection assay and expression of apoptosis-associated proteins.ResultsThe levels of miR-383 were lower while the levels of Bcl-2 levels were higher in GC specimens, compared to tissue from the adjacent non-tumor region. Low miR-383 and high Bcl-2 seemed to be associated with high malignancy and metastasis. In GC specimens, the levels of Bcl-2 and miR-383 inversely correlated. The overall survival of miR-383-low cases was poorer. Mechanistically, miR-383 targeted the 3′-UTR of Bcl-2 mRNA to inhibit its protein translation. Overexpression of miR-383 downregulated Bcl-2, resulting in reduced survival of Fluorouracil-treated GC cells. Similar conclusion was drawn through analysis of published database.ConclusionMiR-383 reduces survival of Fluorouracil-treated GC cells through downregulating of Bcl-2.
Highlights
Anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) plays a substantial role in the carcinogenesis, whereas the regulation for Bcl-2 in gastric carcinoma (GC) is poorly understood
Altered miR-383 and Bcl-2 inversely correlates in GC specimens We analyzed specimens from 50 GC patients TNMstaged II to IV, since we wanted to analyze all cases with similar treatment
Since we planned to analyzed Bcl-2 and miR-383 levels in GC versus paired non-tumor tissue (NT), we first excluded the effects of intra-tumoral inflammatory cells on analysis of total tumor tissue
Summary
Anti-apoptotic protein Bcl-2 plays a substantial role in the carcinogenesis, whereas the regulation for Bcl-2 in gastric carcinoma (GC) is poorly understood. A role of microRNA (miR)-383 in the control of Bcl has not been shown in GC and addressed in the current study. It is expected to be resulting from augmentation of anti-apoptotic potential of GC cells during 5-FU treatment [3,4,5], likely through altered expression of certain apoptosis-associated proteins, such as Bcl-2 [6]. MiR-383 has been shown to inhibit retinal pigment epithelial cell viability and to promote apoptosis and ROS formation likely through B-cell lymphoma 2 (Bcl-2) and peroxiredoxin 3 [14]. MiR-383 upregulation was shown to prevent propofol-induced apoptosis of hippocampal neuron and cognitive impairment via Bcl-2 [15].
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