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RGS5 decreases the proliferation of human ovarian carcinoma?derived primary endothelial cells through the MAPK/ERK signaling pathway in hypoxia.

ABSTRACT: Regulator of G?protein signaling 5 (RGS5), a tissue?speci?c signal?regulating molecule, plays a key role in the development of the vasculature. It was recently found that RGS5 is abundantly expressed in epithelial ovarian cancer (EOC) compared with the normal ovaries. However, the distribution of RGS5 in EOC and its signi?cance require further investigation. The aim of the present study was to investigate the expression of RGS5 in EOC, as well as its association with cancer differentiation, metastasis and clinicopathological parameters. Immunohistochemistry (IHC), western blotting, RT?PCR, wound?healing, cell proliferation and flow cytometric assays were the methods used in the present study. RGS5 was highly expressed in the cytoplasm of ovarian carcinoma cells and in microvascular structures. The expression of RGS5 in EOC was negatively associated with peritoneal metastasis (P=0.004), but it was not found to be associated with age, tumor size, clinical stage or lymph node metastasis (P>0.05). EOC patients with high RGS5 expression had a prolonged progression?free survival (72.34±8.41 vs. 43.56±5.41 months, P<0.001). High expression of RGS5 was correlated with significantly lower microvascular density (MVD) as indicated by the expression of CD34, whereas the opposite was observed in tissues with low RGS5 expression (P<0.05). Hypoxia increased RGS5 expression in ovarian carcinoma?derived endothelial cells (ODMECs), whereas the proliferative capacity of ODMECs exhibited a significant increase following RNAi?mediated reduction of RGS5 expression. These data indicated that RGS5 plays a key role in angiogenesis in ovarian carcinoma. In addition, RGS5 downregulated the expression of the downstream proteins CDC25A, CDK2 and cyclin E, which are mediated by the mitogen?activated protein kinase/extracellular signal?regulated kinase pathway, causing ODMEC arrest in the G1 phase of the cell cycle under hypoxic conditions. Collectively, our data indicated that RGS5 is crucial for the occurrence and development of ovarian cancer, and that RGS5 and its signaling pathway may serve as anti?angiogenesis targets for the treatment of ovarian cancer.

SUBMITTER: Wang D

PROVIDER: S-EPMC6278583 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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RGS5 decreases the proliferation of human ovarian carcinoma‑derived primary endothelial cells through the MAPK/ERK signaling pathway in hypoxia.

Wang Dan D Xu Yan Y Feng Lu L Yin Pin P Song Shuang Shuang SS Wu Feng F Yan Ping P Liang Zhiqing Z

Oncology reports 20181022 1

Regulator of G‑protein signaling 5 (RGS5), a tissue‑speciﬁc signal‑regulating molecule, plays a key role in the development of the vasculature. It was recently found that RGS5 is abundantly expressed in epithelial ovarian cancer (EOC) compared with the normal ovaries. However, the distribution of RGS5 in EOC and its signiﬁcance require further investigation. The aim of the present study was to investigate the expression of RGS5 in EOC, as well as its association with cancer differentiation, meta ...[more]

PMID: 30365142

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Project description:BackgroundAbnormal expression of ribosomal proteins has an important regulatory effect on the progression of cancer. RPL5 is involved in the progression of various malignancies, however, the role of RPL5 in colon cancer remains is still unclear.MethodsData from TCGA and GTEx databases were used to analyze the RPL5 expression in pan-cancer. The expression level of RPL5 in clinical colon cancer tissue samples and human colon cancer cell lines was detected by western blotting; siRNA targeting RPL5 was designed, and its interference efficiency was verified by western blotting and RT-qPCR; CCK8 assay, clone formation assay, cell cycle assay, and cell scratch assay were used to observe the effect of RPL5 on colon cancer cell proliferation and migration; the changes of proteins related to MAPK/ERK signaling pathway were also detected using western blotting.ResultsThe expression level of RPL5 in colon cancer tissues and cell lines was significantly higher than that in adjacent tissues and NCM460 cells, respectively, and its expression level was higher in HCT116 cells and RKO cells. Knockdown of RPL5 significantly inhibited the proliferation and migration of HCT16 and RKO cells, and arrested the cell cycle in G0/G1 phase. Mechanistic studies revealed that the expression of p-MEK1/2, p-ERK, c-Myc were down-regulated, and the expression of FOXO3 was up-regulated after down-regulation of RPL5, ERK activator (TBHQ) could partially reverse the above-mentioned effects caused by siRPL5. Moreover, TBHQ could partially reverse the inhibitory effect of siRPL5 on the proliferation and migration of colon cancer cells. Collectively, RPL5 promoted colon cell proliferation and migration, at least in part, by activating the MAPK/ERK signaling pathway.ConclusionRPL5 promoted colon cell proliferation and migration, at least in part, by activating the MAPK/ERK signaling pathway, which may serve as a novel therapeutic target for cancers in which MAPK/ERK signaling is a dominant feature.

Dataset Information

RGS5 decreases the proliferation of human ovarian carcinoma?derived primary endothelial cells through the MAPK/ERK signaling pathway in hypoxia.

Publications

RGS5 decreases the proliferation of human ovarian carcinoma‑derived primary endothelial cells through the MAPK/ERK signaling pathway in hypoxia.

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