MicroRNA-383 Regulates the Apoptosis of Tumor Cells through Targeting Gadd45g

Abstract

Background MicroRNAs (miRNAs) are a class of small non-coding single-stranded RNA molecules that inhibit gene expression at post-transcriptional level. Gadd45g (growth arrest and DNA-damage-inducible 45 gamma) is a stress-response protein, which has been implicated in several biological processes, including DNA repair, the cell cycle and cell differentiation. Results In this work, we found that miR-383 is a negative regulator of Gadd45g. Forced expression of miR-383 decreased the expression of Gadd45g through binding to the 3′ untranslated region (3′-UTR), whereas inhibition of miR-383 increased Gadd45g expression. The presence of miR-383 increased the cellular sensitivity to DNA damage in breast cancer cells, which was rescued by ectopic expression of Gadd45g without the 3′-UTR. miR-383 also regulates the expression of Gadd45g in embryonic stem (ES) cells, but not their apoptosis under genotoxic stress. miR-383 was further showed to negatively regulate ES cell differentiation via targeting Gadd45g, which subsequently modulates the pluripotency-associated genes. Taken together, our study demonstrates that miR-383 is a negative regulator of Gadd45g in both tumor cells and ES cells, however, has distinct function in regulating cell apoptosis. miR-383 may be used as antineoplastic agents in cancer chemotherapy. Conclusion We demonstrate for the first time that miR-383 can specifically regulates the expression of Gadd45g by directly targeting to the 3-UTR region of Gadd45g mRNA, a regulatory process conserved in human tumor cells and mouse embryonic stem cells. These two compotents can be potentially used as antineoplastic agents in cancer chemotherapy.

Inhibition of MicroRNA-383 Ameliorates Injury After Focal Cerebral Ischemia via Targeting PPARγ

“…Decreased levels of miR-383 in human malignant tumors were shown to inhibit growth, proliferation, migration, and invasion of U85 and U251 cells [28,29]. MiR-383 acts as an antineoplastic agent via regulation of cancer cell apoptosis [30]. In our present study, decreased expression of miR-383 was found at 24h after MCAO.…”

MicroRNA‐383 is a tumor suppressor in human lung cancer by targeting endothelial PAS domain‐containing protein 1

“…Some miRs were also reported to be directly involved in the tumorigenesis of cancer, including lung cancer. For example, miR‐383 was reported to regulate cell apoptosis through targeting Gadd45g in both tumor cells and embryonic stem cells . However, the role of miR‐383 has been controversial, exhibiting distinct, sometimes even opposite, effects on tumorigenesis in different cancers.…”

“…For example, miR-383 was reported to regulate cell apoptosis through targeting Gadd45g in both tumor cells and embryonic stem cells. 9 However, the role of miR-383 has been controversial, exhibiting distinct, sometimes even opposite, effects on tumorigenesis in different cancers. In human epithelial ovarian cancer, miR-383 promoted tumor progress by targeting the caspase-2 gene, therefore inhibiting apoptosis of cancer cells.…”

miR‐383 promotes cholangiocarcinoma cell proliferation, migration, and invasion through targeting IRF1

“…Subsequently, we conducted a luciferase reporter assay to prove the predicted the binding site miR-383 on IRF1 3′-UTR. [23][24][25][26][27] The expression status and clinical value of miR-383 in cholangiocarcinoma still remain unknown. The biological function of miR-383 has been reported in various types of human cancers.…”