Dataset Information

MiR-140-3p Inhibits Cutaneous Melanoma Progression by Disrupting AKT/p70S6K and JNK Pathways through ABHD2.

ABSTRACT: Because cutaneous melanoma (CM) is one of the most lethal human tumors, major treatment advances are vital. miR-140-3p has been suggested to act as a suppressor in a range of malignant tumors, implying its possible use as a biomarker for effective antineoplastic treatment. However, the potential role of miR-140-3p in CM and the underlying mechanism remain unclear. In the present study, we identified lower levels of miR-140-3p in both CM tissues and cell lines; this downregulation was strongly associated with worse CM survival. Additionally, overexpression of miR-140-3p significantly inhibited cell proliferation, migration, and invasion in CM cells with different cell line origins. Importantly, by means of both bioinformatics analysis and luciferase reporter assay, we revealed abhydrolase domain containing 2 (ABHD2) to be a target of miR-140-3p in CM cells. Upregulation of ABHD2 reversed the tumor-suppressive effects of miR-140-3p in CM cells. Furthermore, miR-140-3p-targeted ABHD2 played a role in both activation of JNK signaling and inhibition of the AKT/p70S6K pathway in CM cells. Finally, in vivo results strongly suggested the suppressive effects of miR-140-3p on CM growth and metastasis. Collectively, our findings highlight a novel antineoplastic function for miR-140-3p in CM through ABHD2.

SUBMITTER: He Y

PROVIDER: S-EPMC7163049 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

miR-140-3p Inhibits Cutaneous Melanoma Progression by Disrupting AKT/p70S6K and JNK Pathways through ABHD2.

He Yuanmin Y Yang Yan Y Liao Yongmei Y Xu Jixiang J Liu Li L Li Changqiang C Xiong Xia X

Molecular therapy oncolytics 20200330

Because cutaneous melanoma (CM) is one of the most lethal human tumors, major treatment advances are vital. miR-140-3p has been suggested to act as a suppressor in a range of malignant tumors, implying its possible use as a biomarker for effective antineoplastic treatment. However, the potential role of miR-140-3p in CM and the underlying mechanism remain unclear. In the present study, we identified lower levels of miR-140-3p in both CM tissues and cell lines; this downregulation was strongly as ...[more]

PMID: 32322665

Similar Datasets

Project description:Subretinal fibrosis (SF) is an important cause of submacular neovascularization that leads to permanent vision loss, but has no effective clinical treatment. The present study examined the influence of metformin on SF, and investigated whether the mechanism involves the microRNA (miR)-140-3p/LIN28B/JNK/STAT3-mediated regulation of oxidative stress, angiogenesis and fibrosis-associated indicators. A mouse model of laser-induced SF was established. In addition, an ARPE-19 fibrotic cell model was established using TGF-β1. A Cell Counting Kit-8 assay was used to examine cell viability. Flow cytometry was used to measure reactive oxygen species levels, and western blotting was used to detect the levels of proteins associated with epithelial-mesenchymal transition (EMT), signaling and fibrosis. The levels of superoxide dismutase, malondialdehyde, glutathione-peroxidase and catalase were measured using kits. Scratch assays and Transwell assays were used to assess cell migration and invasion, respectively, and reverse transcription-quantitative PCR was used to determine the levels of miR-140-3p and LIN28B. Dual-luciferase assays were used to verify the targeting relationship between miR-140-3p and LIN28B, and coimmunoprecipitation was used to confirm the interaction between LIN28B and JNK. Masson staining and hematoxylin and eosin staining were used to examine collagenous fibers and the histopathology of eye tissue. In ARPE-19 cells induced by TGF-β1, metformin promoted miR-140-3p expression and inhibited LIN28B expression and JNK/STAT3 pathway activation, thereby inhibiting oxidative stress, EMT and fibrosis in ARPE-19 cells. The overexpression of LIN28B or treatment with the JNK/STAT3 agonist anisomycin partially reversed the inhibitory effect of metformin on oxidative stress and fibrosis in ARPE-19 cells. The dual-luciferase reporter assay and coimmunoprecipitation assay showed that miR-140-3p targeted the 3' untranslated region of LIN28B mRNA and inhibited LIN28B expression. LIN28B targeted and bound to JNK and regulated the JNK/STAT3 pathway. Therefore, it may be concluded that metformin can promote miR-140-3p expression, inhibit LIN28B and then inhibit the JNK/STAT3 pathway to alleviate SF.

Project description:BackgroundUtrophin (UTRN), as a tumor suppressor gene, is involved in various cancer progression. The function of UTRN in the melanoma process and the related molecular mechanisms are still unclear. Herein, we studied the function of UTRN in melanoma growth and the relevant molecular mechanisms.MethodsUsing the GEO database and UCSC Xena project, we compared the expression of UTRN in non-cancerous and melanoma tissues. Immunohistochemistry (IHC) staining, qRT-PCR and Western Blot (WB) were performed to evaluate UTRN expression in clinical samples. A total of 447 cases with UTRN expression data, patient characteristics and survival data were extracted from TCGA database and analyzed. After stable transduction and single cell cloning, the proliferation ability of A375 human melanoma cells was analyzed by Cell Counting Kit‑8 (CCK) and 5‑ethynyl‑2'‑deoxyuridine (EdU) incorporation assays. GSEA was performed to predict the mechanism by which UTRN regulated melanoma growth. Then WB analysis was used to assess the protein expression levels of pathway signaling in overexpression (EXP) melanoma cells. Epac activator 8-pCPT-2'-O-Me-cAMP was then used to evaluate the proliferation ability by activation of p38 and JNK/c-Jun signaling pathways.ResultsData from GEO and UCSC Xena project indicated that UTRN expression was decreased in melanoma. Experiment on clinical samples further confirmed our finding. TCGA results showed that a reduced expression of UTRN in 447 melanoma samples was associated with advanced clinical characteristics (T stage, Clark level, ulceration), shorter survival time and poorer prognosis. In addition, up-regulated UTRN expression inhibited melanoma cell proliferation when compared to control group. MAPK signaling pathway was presented in both KEGG and BioCarta databases by using GSEA tool. WB results confirmed the down-regulated expression of p38, JNK1 and c-Jun in EXP group when compared to control group. Epac activator 8-pCPT-2'-O-Me-cAMP treatment could partially rescue proliferation of tumor cells.ConclusionWe have demonstrated that reduced UTRN predicted poorer prognosis and UTRN inhibited melanoma growth via p38 and JNK1/c-Jun pathways. Therefore, UTRN could serve as a tumor suppressor and novel prognostic biomarker for melanoma patients.

Dataset Information

MiR-140-3p Inhibits Cutaneous Melanoma Progression by Disrupting AKT/p70S6K and JNK Pathways through ABHD2.

Publications

miR-140-3p Inhibits Cutaneous Melanoma Progression by Disrupting AKT/p70S6K and JNK Pathways through ABHD2.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets