Dataset Information

MiR-152-3p Affects the Progression of Colon Cancer via the KLF4/IFITM3 Axis.

ABSTRACT: Objective:The purpose of this study was to investigate the relationship between miR-152-3p and the KLF4/IFITM3 axis, thereby revealing the mechanism underlying colon cancer occurrence and development, consequently providing a promising target for colon cancer treatment. Methods:Bioinformatics methods were implemented to analyze the differential expression of miRNAs and mRNAs in colon cancer, confirm the target miRNA, and predict the downstream targeted mRNAs. qRT-PCR and Western blot were performed to detect the expression of miR-152-3p, KLF4, and IFITM3. CCK-8 and colony formation assays were conducted for the assessment of cell proliferation, and flow cytometry was carried out for the detection of cell apoptosis. Finally, dual-luciferase reporter gene assay was employed to verify the targeting relationship between miR-152-3p and KLF4. Results:miR-152-3p was highly expressed in colon cancer cells, whereas KLF4 was poorly expressed. Dual-luciferase assay verified that miR-152-3p targeted to bind to KLF4 and suppressed its expression. Moreover, silencing miR-152-3p or overexpressing KLF4 was found to downregulate IFITM3, thereby inhibiting cell proliferation and potentiating cell apoptosis. In rescue experiments, we found that miR-152-3p deficiency decreased the expression of IFITM3 and weakened cancer cell proliferation, and such effects were restored when miR-152-3p and KLF4 were silenced simultaneously. Conclusion:In sum, we discovered that miR-152-3p can affect the pathogenesis of colon cancer via the KLF4/IFITM3 axis.

SUBMITTER: Zhu X

PROVIDER: S-EPMC7481932 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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miR-152-3p Affects the Progression of Colon Cancer via the KLF4/IFITM3 Axis.

Zhu Xiaoyi X Shen Zhan Z Man Da D Ruan Hang H Huang Sha S

Computational and mathematical methods in medicine 20200901

<h4>Objective</h4>The purpose of this study was to investigate the relationship between miR-152-3p and the KLF4/IFITM3 axis, thereby revealing the mechanism underlying colon cancer occurrence and development, consequently providing a promising target for colon cancer treatment.<h4>Methods</h4>Bioinformatics methods were implemented to analyze the differential expression of miRNAs and mRNAs in colon cancer, confirm the target miRNA, and predict the downstream targeted mRNAs. qRT-PCR and Western b ...[more]

PMID: 32952601

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Project description:BackgroundColorectal cancer (CRC) is the leading cause of cancer-related death worldwide. Exosome shave emerged as crucial regulators of intercellular communication and that abundant Circular RNAs (circRNAs) are enriched within exosomes. CircRNAs are novel members of noncoding RNAs regulating cancer proliferation and progression. However, the function and regulatory mechanism of cancer-derived exosomal circRNAs in CRC remains unclear.MethodsCRC cells-derived exosomes were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA) and western blot. CCK-8, wound healing and transwell assays, and flow cytometry assays were conducted to assess whether exosomes would affect the proliferation, metastasis, and apoptosis of CRC cells, respectively. Moreover, we performed the RNA sequencing and RT-qPCR to identify circRNAs in exosome-stimulated CRC cells. Fluorescence in situ hybridization (FISH) assay was used to detect the cellular distribution of circPACRGL. Bioinformatic analyses (StarBase 2.0) were used to pool the miRNA targets of circPACRGL. Luciferase assays were performed to verify the direct interaction. Finally, flow cytometry was used to detect the differentiation of N1-N2 neutrophils.ResultsOur study identified a novel CRC-derived exosomal circRNA, circPACRGL. We found circPACRGL was significantly upregulated in CRC cells after tumor-derived exosomes addition. Moreover, circPACRGL serves as a sponge for miR-142-3p/miR-506-3p to facilitate the transforming growth factor-β1 (TGF-β1) expression. As a result, circPACRGL promoted CRC cell proliferation, migration and invasion, as well as differentiation of N1 to N2 neutrophils via miR-142-3p/miR-506-3p-TGF-β1 axis.ConclusionOur study, the first to reveal that cancer-derived exosomal circPACRGL plays an oncogenic role in CRC proliferation and metastasis, providing mechanistic insights into the roles of circRNAs in CRC progression and a valuable marker for CRC treatment.

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Dataset Information

MiR-152-3p Affects the Progression of Colon Cancer via the KLF4/IFITM3 Axis.

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miR-152-3p Affects the Progression of Colon Cancer via the KLF4/IFITM3 Axis.

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