MicroRNA-383-5p inhibits the progression of gastric carcinoma via targeting HDAC9 expression

Abstract

MicroRNAs (miRNAs), as post-transcriptional regulators, have been reported to be involved in the initiation and progression of various types of cancer, including gastric cancer (GC). The present study aimed to investigate the role of miR-383-5p in gastric carcinogenesis. Cell viability was analyzed using CCK-8 kit. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to evaluate cell apoptosis. The expression levels of miR-383-5p and histone deacetylase 9 (HDAC9) mRNA in GC tissues and cell lines were analyzed using RT-qPCR. The protein expression of HDAC9 was detected by western blotting. We found that HDAC9 was up-regulated and miR-383-5p was down-regulated in GC tissues and cell lines. High HDAC9 expression or low miR-383-5p expression was closely related to poor prognosis and metastasis in GC patients. HDAC9 knockout or miR-383-5p mimics led to growth inhibition and increased apoptosis in AGS and SGC-7901 cells. More importantly, we validated that miR-383-5p as a post-transcriptional regulator inhibited HDAC9 expression and was inversely correlated with HDAC9 expression in GC tissues. miR-383-5p had the opposite effects to HDAC9 in gastric carcinogenesis. miR-383-5p played an important role in gastric carcinogenesis, and it is one of the important mechanisms to regulate oncogenic HDAC9 in GC, which might be helpful in the development of novel therapeutic strategies for the treatment of GC.

<p>Long Noncoding RNA <em>FGD5-AS1</em> Acts as a Competing Endogenous RNA on microRNA-383 to Enhance the Malignant Characteristics of Esophageal Squamous Cell Carcinoma by Increasing SP1 Expression</p>

“…MiR-383 exerts important actions on the progression of various human cancers. For example, miR-383 is underexpressed in gastric cancer, 23,24 thyroid cancer, 25 hepatocellular carcinoma, 25 and ovarian cancer. 26 Functionally, miR-383 serves as a tumor-suppressive miRNA in the abovementioned human cancer types.…”

“…The latter was chosen for experimental verification because this miRNA has frequently been implicated in multiple types of human tumors. [23][24][25][26][27] The luciferase reporter assay was performed to test whether miR-383 can directly bind to FGD5-AS1 in ESCC cells. Either reporter plasmid FGD5-AS1-wt or FGD5-AS1-mut was transfected into TE-1 and Eca109 cells along with either agomir-383 or agomir-NC.…”

microRNA‐665 is down‐regulated in gastric cancer and inhibits proliferation, invasion, and EMT by targeting PPP2R2A

“…Thus, miRNAs are thought to be markers of cancers diagnosis, progression, and prognosis . Many human miRNAs have been confirmed to be dysregulated in GC, including miR‐32‐5p, miR‐544a, miR‐1297, miR‐625, and miR‐383‐5p . Up to now, miR‐665 has been reported to function as an oncogene in breast cancer, hepatocellular carcinoma, acute lymphoblastic leukaemia, or function as a tumour suppressor in colorectal cancer, cervical cancer, and ovarian cancer; the functions of miR‐665 in GC were rare unexplored previously.…”

HDAC9 Is Preferentially Expressed in Dedifferentiated Hepatocellular Carcinoma Cells and Is Involved in an Anchorage-Independent Growth

“…In endothelial cells, HDAC9 is induced via signal transducer and activator of transcription 3 (STAT3) signaling to proliferate by PDAC-secreted proangiogenic factors [ 24 ]. HDAC9 is reported to be regulated post-transcriptionally by several micro RNAs in retinal, oral, breast, and gastric cancer, and as being associated with poor prognosis [ 21 , 23 , 25 , 26 ]. Analysis of other signaling pathways that induce dedifferentiation and malignant phenotype via HDAC9 may help us to understand the essential role of HDAC9 in tumor dedifferentiation.…”