Dataset Information

MiR141 Proteomic profile in Ovarian Cancer

ABSTRACT: Over the last two decades, mounting evidence has demonstrated the aberrant expression of miRNAs in different human malignancies, including ovarian carcinomas. In this study, we found that miR-141 were secreted by ovarian cancer cells and transferred to the stromal cells by exosomal pathway. To clarify the mechanisms that miR-141 remodeling stromal fibroblast and reprogramming the relevant signals, miR-141 were overexpressed in WPMY-1 and their respective scrambled control were send for proteomic analysis.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stromal Cell Of Ovarian Cortex

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: Xueyu WANG

LAB HEAD: Dr. David W. CHAN

PROVIDER: PXD026929 | Pride | 2023-03-11

REPOSITORIES: Pride

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Publications

Tumor-secreted exosomal miR-141 activates tumor-stroma interactions and controls premetastatic niche formation in ovarian cancer metastasis.

Mo Yulan Y Leung Leanne L LL Mak Celia S L CSL Wang Xueyu X Chan Wai-Sun WS Hui Lynn M N LMN Tang Hermit W M HWM Siu Michelle K Y MKY Sharma Rakesh R Xu Dakang D Tsui Stephen K W SKW Ngan Hextan Y S HYS Yung Mingo M H MMH Chan Karen K L KKL Chan David W DW

Molecular cancer 20230109 1

<h4>Background</h4>Metastatic colonization is one of the critical steps in tumor metastasis. A pre-metastatic niche is required for metastatic colonization and is determined by tumor-stroma interactions, yet the mechanistic underpinnings remain incompletely understood.<h4>Methods</h4>PCR-based miRNome profiling, qPCR, immunofluorescent analyses evaluated the expression of exosomal miR-141 and cell-to-cell communication. LC-MS/MS proteomic profiling and Dual-Luciferase analyses identified YAP1 as ...[more]

PMID: 36624516

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Project description:Background & Aims: Extracellular vesicles (EVs) play a pivotal role in connecting tumor cells and their local and distant microenvironment. Here, we aimed to understand the role and molecular basis of patient-derived EVs in modulating cancer stemness and tumorigenesis in the context of hepatocellular carcinoma (HCC). Methods: EVs were isolated, quantified and characterized from patients’ sera. EVs were tested vigorously, both in vitro and in vivo, by various functional assays. Proteomic analysis was performed to identify the functional components of EVs. The expression level of polymeric immunoglobulin receptor (pIgR) in circulating EVs, tumor and non-tumorous tissues of HCC patients was determined by ELISA, immunoblotting, immunohistochemistry and quantitative PCR. The functional role and underlying mechanism of EVs with an enhanced pIgR expression was elucidated. Blockage of EV-pIgR with neutralizing antibody was performed in nude mice implanted with patient-derived tumor xenograft (PDTX). Results: Circulating EVs of late-stage HCC (L-HCC) patient had significantly elevated pIgR expression when compared to the EVs released by control individuals. The augmenting effect of L-HCC patient in cancer stemness and tumorigenesis was hindered by anti-pIgR antibody. EVs enriched with pIgR consistently promoted cancer stemness and cancerous phenotypes in the recipient cells. Mechanistically, EV-pIgR-induced cancer aggressiveness was abrogated by Akt and β-catenin inhibitors, ascertaining the role of EV-pIgR through the activation of PDK1/Akt/GSK3β/β-catenin signaling axis. Furthermore, anti-pIgR neutralizing antibody attenuated the tumor growth in mice implanted with PDTX. Conclusion: The study illustrates an unrevealed role of EV-pIgR in regulating cancer stemness and aggressiveness, in which EV-pIgR activates PDK1/Akt/GSK3β/β-catenin signaling cascades. The blockage of intercellular communications mediated by EV-pIgR in the tumor microenvironment may provide a new therapeutic strategy for cancer patients.

Dataset Information

MiR141 Proteomic profile in Ovarian Cancer

Publications

Tumor-secreted exosomal miR-141 activates tumor-stroma interactions and controls premetastatic niche formation in ovarian cancer metastasis.

Similar Datasets

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