Exosomal miR-21-5p derived from gastric cancer promotes peritoneal metastasis via mesothelial-to-mesenchymal transition

Li, Qiang; Li, Bowen; Li, Qing; Wei, Song; He, Zhongyuan; Huang, Xiaoxu; Wang, Lu; Xia, Yiwen; Xu, Zhipeng; Li, Zheng; Wang, Weizhi; Yang, Li; Zhang, Diancai; Xu, Zekuan

doi:10.1038/s41419-018-0928-8

Cited by 166 publications

(136 citation statements)

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“…It is reported that miRNA is involved in tumorigenesis, acting variously as either oncogenes [24][25][26][27] or tumor suppressors. 16,28,29 Increasing evidence has demonstrated that miRNAs are effective biomarkers and tumor regulators in kidney cancer and therefore have broad implications in both clinical and therapeutic practice.…”

Section: Discussionmentioning

confidence: 99%

<p>MiR-935 Promotes Clear Cell Renal Cell Carcinoma Migration and Invasion by Targeting IREB2</p>

Liu

Chen

et al. 2019

CMAR

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Purpose: Clear cell renal cell carcinoma (ccRCC) has the highest rate of metastasis and invasion in RCC and is the third most common adult urinary malignancy. miRNA may serve a critical role in human cancer development and progression, has been confirmed to play a pivotal role in RCC cell invasion and migration. Since miR-935 had been verified to be an oncogene or tumor suppressor in various cancers, the role of miR-935 in RCC was unclear. Methods: Real-time quantitative polymerase chain reaction (qRT-PCR) was used to verify miR-935 expression. CCK-8 assay, wound healing assay and transwell assay were used to investigate the cell proliferation, migration and invasion of miR-935. Receiver operating characteristic (ROC) curve analysis was applied to discriminate different clinical classifications. Gain or loss of function approaches were used to investigate the cell proliferation, migration and invasion of miR-935 in vitro. Bioinformatics analysis and dual-luciferase reporter assay were used to identify the target of miR-935. Results: MiR-935 had a higher expression level in RCC cells and cancer tissues. MiR-935 mimics promoted cell proliferation, migration and invasion, and miR-935 inhibitor inhibited cell inhibit malignancy of cancer cells. Bioinformatics analysis and dual-luciferase reporter assay identified iron-responsive element-binding protein 2 (IREB2) as a direct target of miR-935. qRT-PCR showed IREB2 expression was downregulated in ccRCC cancer tissues and high IREB2 expression had a longer overall survival (OS) and disease-free survival (DFS). Silencing IREB2 could reverse the function of miR-935 inhibitor on cell proliferation and metastasis in renal cancer cells. Conclusion: The study indicated that miR-935 may act as an oncomiRNA and influenced migration and invasion progress of ccRCC by targeting IREB2. Oncogene miR-935 may be a molecular marker and uncover new strategies for ccRCC.

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Section: Discussionmentioning

confidence: 99%

<p>MiR-935 Promotes Clear Cell Renal Cell Carcinoma Migration and Invasion by Targeting IREB2</p>

Liu

Chen

et al. 2019

CMAR

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“…It has been reported that mesothelial cells showed increased vimentin and αSMA expressions and decreased E‐cadherin expression during the MMT process . Therefore, immunoreactivity of a human mesothelial cell line (Met‐5A) separately cocultured with NIH3T3‐miR‐21‐mimic (Figure A) was studied.…”

Section: Resultsmentioning

confidence: 49%

“…In peritoneal dissemination, the MMT is important in the cancer microenvironment . To assess whether the MMT is also observed in the cancer microenvironment in pleural dissemination, surgically resected pleural disseminated nodules of lung adenocarcinomas were studied (Figure A‐C) by double‐staining immunohistochemistry using calretinin, desmin, and αSMA.…”

Section: Resultsmentioning

confidence: 99%

“…This is the first report to examine EVs from pleural lavage fluid, although there are some studies isolating EVs from peritoneal malignant ascites or peritoneal lavage fluid in abdominal organ cancers such as gastric cancer . These previous studies demonstrated that EVs associated with cancer cells in the peritoneal cavity can be prognostic factors, and they function to promote peritoneal dissemination . The present studies demonstrated that the EV‐miR‐21 expression level in pleural lavage fluid reflected not only cytopathological positivity for cancer cells in pleural lavage fluid, but also the degree of pleural invasion at the primary sites.…”

Section: Discussionmentioning

confidence: 99%

“…However, both metastatic and premetastatic niches in the dissemination pathway are not fully understood. In peritoneal dissemination, it has been reported that cancer‐associated fibroblasts (CAFs), among the representative components of the cancer microenvironment, were derived from mesothelial cells via the mesothelial to mesenchymal transition (MMT) . On the other hand, mechanisms of pleural dissemination remain unclear.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Clinicopathological significance of microRNA‐21 in extracellular vesicles of pleural lavage fluid of lung adenocarcinoma and its functions inducing the mesothelial to mesenchymal transition

et al. 2020

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Background: Pre-resection pleural lavage cytology is useful to predict tumor recurrence and the prognosis of lung cancer patients. Recently, extracellular vesicles (EVs) isolated from effusion specimens have come under the spotlight, and several studies showed that microRNA in EVs is associated with prognosis. MicroRNA-21 (miR-21) is a representative onco-microRNA, and miR-21 in EVs (EV-miR-21) promotes cancer dissemination by inducing mesothelial to mesenchymal transition (MMT) in the peritoneal cavity. In this study, we isolated EVs from pleural lavage fluid and focused on EV-miR-21 as a diagnostic factor with a relationship to pleural dissemination. Methods: The Cancer Genome Atlas dataset comprising of 448 cases of lung adenocarcinoma, tissue microarray of 144 cases of lung adenocarcinoma, and pleural lavage fluid of 41 cases was used to examine miR-21 expression levels. The function of EV-miR-21 was investigated in vitro. Results: The miR-21 expression level in primary sites was associated with a poor prognosis and correlated with pleural invasion of adenocarcinoma. EV-miR-21 levels in pleural lavage fluid were associated with positive cytology and pleural invasion in the primary sites, even in cytology-negative cases. In vitro studies demonstrated that EV-miR-21 induces the MMT. Mesothelial cells in the MMT showed functions similar to cancer-associated fibroblasts, which are an important stromal component in primary sites and disseminated pleural lesions. Conclusions: EV-miR-21 in pleural lavage fluid is important as a diagnostic and prognostic factor. Moreover, EV-miR-21 induces the MMT, which can form premetastatic niches of dissemination in the pleural cavity. K E Y W O R D S dissemination, exosome, extracellular vesicles, mesothelial to mesenchymal transition, microRNA-21, pleural lavage fluid 2880 | WATABE ET Al.

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Nucleic Acid Amplification Circuit‐Based Hydrogel (NACH) Assay for One‐Step Detection of Metastatic Gastric Cancer‐Derived Exosomal miRNA

Seo,

Lim,

Kim

et al. 2024

Advanced Science

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Gastric cancer (GC) is recognized as the fifth most prevalent malignant tumor worldwide. It is characterized by diverse clinical symptoms, treatment responses, and prognoses. In GC prognosis, the promotion of epithelial–mesenchymal transition (EMT) fosters cancer cell invasion and metastasis, thereby triggering the dissemination of tumor cells. This study proposes a nucleic acid amplification circuit‐based hydrogel (NACH) assay for identifying exosomal miRNA derived from metastatic GC. The NACH assay employs the rolling circle amplification method and targets miRNA‐21, a tumor‐related oncogene, and miRNA‐99a, which promotes EMT. Specific amplification probes for each target are immobilized within the hydrogel, enabling a streamlined, one‐step amplification reaction. The NACH assay exhibits a detection limit of 1 fm for miRNA‐21 and miRNA‐99a, thereby enabling rapid and highly sensitive on‐site detection. Performance evaluation using exosomal miRNA extracted from cell culture media, mouse plasma, and human plasma revealed fluorescence intensity patterns similar to those obtained in qRT‐PCR. Furthermore, deploying a custom‐developed portable fluorometer for the NACH assay allows for diagnostic performance assessment and point‐of‐care testing using clinical samples from GC patients. These findings emphasize the potential of the NACH assay to be used as a robust tool for the genetic diagnosis of GC based on exosome detection.

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Exosomal miR-21-5p derived from gastric cancer promotes peritoneal metastasis via mesothelial-to-mesenchymal transition

Cited by 166 publications

References 47 publications

<p>MiR-935 Promotes Clear Cell Renal Cell Carcinoma Migration and Invasion by Targeting IREB2</p>

<p>MiR-935 Promotes Clear Cell Renal Cell Carcinoma Migration and Invasion by Targeting IREB2</p>

Clinicopathological significance of microRNA‐21 in extracellular vesicles of pleural lavage fluid of lung adenocarcinoma and its functions inducing the mesothelial to mesenchymal transition

Nucleic Acid Amplification Circuit‐Based Hydrogel (NACH) Assay for One‐Step Detection of Metastatic Gastric Cancer‐Derived Exosomal miRNA

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