miR-92b-3p acts as a tumor suppressor by targeting Gabra3 in pancreatic cancer

Abstract

BackgroundMicroRNAs (miRNAs) can act as oncogenes or tumor suppressors by controlling cell proliferation, differentiation, metastasis and apoptosis, and miRNA dysregulation is involved in the development of pancreatic cancer (PC). Our previous study demonstrated that Gabra3 plays critical roles in cancer progression. However, whether Gabra3 is regulated by miRNAs in PC remains unknown.MethodsThe expression levels of miR-92b-3p and Gabra3 were measured by quantitative PCR (qPCR), immunoblotting, in situ hybridization (ISH) and immunohistochemistry (IHC). The proliferation rate of PC cells was detected by MTS assay. Wound-healing and transwell assays were used to examine the invasive abilities of PC cells. Dual-luciferase reporter assays were used to determine how miR-92b-3p regulates Gabra3. Xenograft mouse models were used to assess the role of miR-92b-3p in PC tumor formation in vivo.ResultsHere, we provide evidence that miR-92b-3p acted as a tumor suppressor in PC by regulating Gabra3 expression. MiR-92b-3p expression levels were lower in PC tissues than corresponding noncancerous pancreatic (CNP) tissues and were associated with a poor prognosis in PC patients. MiR-92b-3p overexpression suppressed the proliferation and invasion of PC cells in both in vivo and in vitro models. Conversely, miR-92b-3p knockdown induced an aggressive phenotype in PC cells. Mechanistically, miR-92b-3p overexpression suppressed Gabra3 expression, which then led to the inactivation of important oncogenic pathways, including the AKT/mTOR and JNK pathways.ConclusionOur results suggest that miR-92b-3p acted as a tumor suppressor by targeting Gabra3-associated oncogenic pathways; these results provide novel insight into future treatments for PC patients.Electronic supplementary materialThe online version of this article (10.1186/s12943-017-0723-7) contains supplementary material, which is available to authorized users.

microRNA 92b-3p regulates primordial follicle assembly by targeting TSC1 in neonatal mouse ovaries

“…As a member of miR-92b cluster, miR-92b-3p was reported to be upregulated in metastatic colorectal carcinoma and targets tumor suppressor F-box and WD-40 domain protein 7 (FBXW7/hCdc4) [22]. However, in pancreatic cancers, it acts as a tumor suppressor by targeting Gabra3 [23], indicating a diverse role of miR-92b-3p in the regulation of different tumor progress. In addition to its roles in tumors, miR-92b-3p also mediates the proliferation and cell cycle progression of pulmonary artery smooth muscles [24], or regulates cardiac hypertrophic growth [25].…”

MicroRNA‐92b‐3p is a prognostic oncomiR that targets TSC1 in clear cell renal cell carcinoma

“…In nonsmall‐cell lung cancer, miR‐92b‐3p directly targets PTEN , promotes cell growth, and induces cisplatin chemosensitivity . However, miR‐92b‐3p has also been reported to act as a tumor suppressor miRNA . The present study shows for the first time that miR‐92b‐3p functions as an oncomiR in both RCC cell lines and ccRCC clinical specimens.…”

“…MicroRNA‐92b‐3p is one of the upregulated miRNAs in ccRCC tissues, according to our previous study, and it has been revealed as an oncomiR in colorectal carcinoma and gastric cancer . In contrast, miR‐92b‐3p might also function as a tumor suppressor RNA in pancreatic cancer . Hence, the physiological role of miR‐92b‐3p varies according to the types of cancer, and the precise mechanism of miR‐92b‐3p in ccRCC progression remains unknown.…”

miR‐365 regulates liver cancer stem cells via RAC1 pathway

“…miRNAs, a small non‐coding RNA molecule (containing about 22 nucleotides), regulate RNA silencing and post‐transcriptional of gene expression in general by binding to the 3′UTR of target mRNAs . miRNAs act as oncogenes or tumor suppressors in tumors dependent on special conditions . miRNAs are also involved in regulating the progression of cancers and CSCs .…”

“…9,10 miRNAs act as oncogenes or tumor suppressors in tumors dependent on special conditions. 11,12 miRNAs are also involved in regulating the progression of cancers and CSCs. 13,14 For instance, miR-429 drives liver tumor-initiating cell properties by targeting Rb binding protein 4.…”