Dataset Information

MiR-509-3p is oncogenic, targets the tumor suppressor PHLPP2, and functions as a novel tumor adjacent normal tissue based prognostic biomarker in colorectal cancer.

ABSTRACT:

Background

Recently the role of microRNAs has been explored immensely as novel regulators and potential biomarkers in several cancers. MiR-509-3p is one such miRNA that has been observed to show a mixed expression in different cancers, while it's expression and clinical relevance in colorectal cancer (CRC) has not yet been characterized.

Methods

We used quantitative PCR to evaluate the expression of miR-509-3p in fresh-frozen CRC tumor tissues and the corresponding tumor-adjacent normal (NAT) tissues from 103 patients. Subsequently, functional studies were performed to further interpret the role of the miRNA in CRC.

Results

MiR-509-3p was found to be overexpressed in CRC tissues in nearly 80% of cases and was associated with an aggressive disease presentation. Notably, a higher expression of the miRNA promoted cell proliferation, migration, and invasion of CRC cells in in vitro and in vivo models. Mechanistically, we confirmed that miR-509-3p directly binds the 3'UTR of the tumor suppressor PHLPP2 and inhibits its expression. Furthermore, within the previous 103 clinical tissue specimens, we observed an overexpression of miR-509-3p within the NAT tissue of patients associated with a poor disease prognosis. Using multivariate analysis, it was observed that the expression of miR-509-3p within the NAT tissue was an independent predictor of prognosis in CRC. At the cellular level, through indirect coculture experiments, miR-509-3p was observed to regulate the proliferative, migratory, and invasive behavior of normal colon cells.

Conclusion

MiR-509-3p strongly contributes to the development and progression of CRC and can potentially function as a prognostic biomarker in the disease.

SUBMITTER: Iyer DN

PROVIDER: S-EPMC8969217 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

MiR-509-3p is oncogenic, targets the tumor suppressor PHLPP2, and functions as a novel tumor adjacent normal tissue based prognostic biomarker in colorectal cancer.

Iyer Deepak Narayanan DN Foo Dominic Chi-Chung DC Lo Oswens Siu-Hung OS Wan Timothy Ming-Hun TM Li Xue X Sin Ryan Wai-Yan RW Pang Roberta Wen-Chi RW Law Wai-Lun WL Ng Lui L

BMC cancer 20220331 1

<h4>Background</h4>Recently the role of microRNAs has been explored immensely as novel regulators and potential biomarkers in several cancers. MiR-509-3p is one such miRNA that has been observed to show a mixed expression in different cancers, while it's expression and clinical relevance in colorectal cancer (CRC) has not yet been characterized.<h4>Methods</h4>We used quantitative PCR to evaluate the expression of miR-509-3p in fresh-frozen CRC tumor tissues and the corresponding tumor-adjacent ...[more]

PMID: 35361144

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Project description:BackgroundGain-of-function mutations and overexpression of KIT are characteristic features of gastrointestinal stromal tumor (GIST). Dysregulation in miRNA expression may lead to KIT overexpression and tumorigenesis.MethodsmiRNA microarray analysis and real-time PCR were used to determine the miRNA expression profiles in a cohort of 69 clinical samples including 50 CD117IHC+/KITmutation GISTs and 19 CD117IHC-/wild-type GISTs. GO enrichment and KEGG pathway analyses were performed to reveal the predicted targets of the dysregulated miRNAs. Of the dysregulated miRNAs whose expression was inversely correlated with that of KIT miRNAs were predicted by bioinformatics analysis and confirmed by luciferase reporter assay. Cell counting kit-8 (CCK-8) and flow cytometry were used to measure the cell proliferation, cycle arrest and apoptosis. Wound healing and transwell assays were used to evaluate migration and invasion. A xenograft BALB/c nude mouse model was applied to investigate the tumorigenesis in vivo. Western blot and qRT-PCR were used to investigate the protein and mRNA levels of KIT and its downstream effectors including ERK, AKT and STAT3.ResultsOf the six miRNAs whose expression was inversely correlated with that of KIT, we found that miR-148b-3p was significantly downregulated in the CD117IHC+/KITmutation GIST cohort. This miRNA was subsequently found to inhibit proliferation, migration and invasion of GIST882 cells. Mechanistically, miR-148b-3p was shown to regulate KIT expression through directly binding to the 3'-UTR of the KIT mRNA. Restoration of miR-148b-3p expression in GIST882 cells led to reduced expression of KIT and the downstream effectors proteins ERK, AKT and STAT3. However, overexpression of KIT reversed the inhibitory effect of miR-148b-3p on cell proliferation, migration and invasion. Furthermore, we found that reduced miR-148b-3p expression correlated with poor overall survival (OS) and disease-free survival (DFS) in GIST patients.ConclusionmiR-148b-3p functions as an important regulator of KIT expression and a potential prognostic biomarker for GISTs.

Dataset Information

MiR-509-3p is oncogenic, targets the tumor suppressor PHLPP2, and functions as a novel tumor adjacent normal tissue based prognostic biomarker in colorectal cancer.

Background

Methods

Results

Conclusion

Publications

MiR-509-3p is oncogenic, targets the tumor suppressor PHLPP2, and functions as a novel tumor adjacent normal tissue based prognostic biomarker in colorectal cancer.

Similar Datasets

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