Dataset Information

RGS19 upregulates Nm23-H1/2 metastasis suppressors by transcriptional activation via the cAMP/PKA/CREB pathway.

ABSTRACT: The Nm23 metastasis suppressor family is involved in physiological and pathological processes including tumorigenesis and metastasis. Although the inverse correlation of Nm23 level with tumor metastasis potential has been widely observed, the mechanisms that regulate the expression of Nm23 remain poorly understood. Our previous studies have revealed that Nm23-H1/2 isoforms are upregulated by RGS19, a regulator of G protein signaling (RGS) protein which accelerates the termination of Gi signals. Here, we examined the ability of RGS19 to stimulate transcriptional regulation of Nm23 by screening a panel of luciferase reporter genes. Transient and stable overexpression of RGS19 upregulated the Nm23-H1/2 protein levels and activated several transcription factors including CREB, AP-1 and SRE in HEK293 cells. Interestingly, agents that increase the intracellular cAMP level and the phosphorylation of CREB (e.g., adrenergic receptor agonist, forskolin, and cAMP analogues) upregulated the expression of Nm23-H1/2 in HEK293 cells and several cancer cell lines including A549, HeLa, MDA-MB-231, and MDA-MB-435s cells. Conversely, inhibition of protein kinase A (PKA) by H-89 suppressed the phosphorylation of CREB and reduced the expression of Nm23-H1/2. Furthermore, activation of PKA attenuated cancer cell migration in wound healing and transwell assays. Collectively, these results revealed a PKA-dependent mechanism for controlling Nm23-H1/2 expression.

SUBMITTER: Li Y

PROVIDER: S-EPMC5642529 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

RGS19 upregulates Nm23-H1/2 metastasis suppressors by transcriptional activation via the cAMP/PKA/CREB pathway.

Li Yuanjun Y Song Jiaxing J Tong Yao Y Chung Sookja Kim SK Wong Yung H YH

Oncotarget 20170722 41

The Nm23 metastasis suppressor family is involved in physiological and pathological processes including tumorigenesis and metastasis. Although the inverse correlation of Nm23 level with tumor metastasis potential has been widely observed, the mechanisms that regulate the expression of Nm23 remain poorly understood. Our previous studies have revealed that Nm23-H1/2 isoforms are upregulated by RGS19, a regulator of G protein signaling (RGS) protein which accelerates the termination of G<sub>i</sub ...[more]

PMID: 29050254

Similar Datasets

Project description:BackgroundNm23-H1 gene has been found to be an inhibitor of tumor metastasis in lung cancer. MicroRNAs (miRNAs) play key roles in tumor metastasis through multiple signaling pathways. This study explored whether the nm23-H1 gene could inhibit invasion and metastasis of lung cancer cells by regulating miRNA-660-5p targets.MethodsQuantitative real-time PCR (qRT-PCR) and western blots were used to measure the expression of nm23-H1 and miR-660-5p of various human lung cancer cell lines. Cell counting kit-8 (CCK-8), wound-healing and transwell assay were carried out to assess cell proliferation, migration and invasion of each cell line. Xenograft were applied to determine in vivo effects of miR-660-5p among nude mice. Luciferase assay and western blot were performed to determine the target gene of miR-660-5p.ResultsWe found that high expression of nm23-H1 correlated with decreased miRNA-660-5p expression. Inhibiting miR-660-5p suppressed lung cancer cells progression significantly in vitro, whereas overexpression of miR-660-5p facilitated tumor growth and bone metastasis in vivo. In addition, as the potential target gene of miR-660-5p, SMARCA5 overexpression in vitro suppressed tumor progression and osteolytic metastasis associated RANKL signaling, which is congruent with the effect of nm23-H1 on the lung cancer cells.ConclusionNm23-H1 inhibits tumor progression and bone-specific metastasis of lung cancer by regulating miR-660-5p/SMARCA5/RANKL axis, which indicates the related genes may serve as potential targets for the treatment of human lung cancer.Key pointsSignificant findings of the study High expression of nm23-H1 correlated with decreased miRNA-660-5p expression. Further, downregulation of miR-660-5p significantly suppressed the tumor progression and bone-specific metastasis of lung cancer cells. What this study adds This is the first study to show an inverse association between nm23-H1 and miR-660-5p, and confirm that nm23-H1 inhibits tumor progression and bone-specific metastasis of lung cancer by regulating miR-660-5p/SMARCA5/RANKL axis.

Dataset Information

RGS19 upregulates Nm23-H1/2 metastasis suppressors by transcriptional activation via the cAMP/PKA/CREB pathway.

Publications

RGS19 upregulates Nm23-H1/2 metastasis suppressors by transcriptional activation via the cAMP/PKA/CREB pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets