MiR-21-5p-driven gene expression in human colorectal DLD-1 cells.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE136665 | GEO | 2019/08/31
REPOSITORIES: GEO
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Project description:miR-21-5p-driven gene expression in human colorectal DLD-1 cells.
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Project description:The aim was to look for target genes of miR-15a-5p or miR-21-5p.
2021-02-11 | E-MTAB-8776 | biostudies-arrayexpress
Project description:Aims This study investigated the impact of hepatocyte exosomes on hepatic stellate cell (HSC) activation and their potential role in liver fibrosis while elucidating the underlying molecular mechanisms. Methods L02 exosomes were extracted, and their influence on LX-2 activation was preliminarily investigated. A mouse liver fibrosis model was established through intraperitoneal injection of 20% carbon tetrachloride (CCl4). Normal and fibrotic hepatocyte exosomes were separately collected to explore their distinct effects on HSC activation. High-throughput sequencing identified differential miRNAs in exosomes from normal and fibrotic hepatocytes. MiR-21-5p, displaying the most substantial expression difference, was selected to assess the correlation between serum exosomal miR-21-5p and liver fibrosis. The target gene of miR-21-5p was validated using a dual luciferase assay. LX-2 cells were transfected with miR-21-5p mimics and inhibitors to clarify the impact and mechanisms of miR-21-5p on HSC activation, proliferation, and collagen synthesis. Results Normal L02 exosomes were internalized by LX-2 cells and inhibited their activation. In comparison to normal hepatocyte exosomes, fibrotic hepatocyte exosomes induced HSC activation. High-throughput sequencing revealed 32 upregulated and 6 downregulated miRNAs in fibrotic hepatocyte exosomes, with the most significant increase observed in miR-21-5p. Serum exosomal miR-21-5p displayed a close association with liver fibrosis. Dual luciferase assays and cell transfection experiments confirmed that miR-21-5p promoted HSC activation, proliferation, and collagen synthesis by targeting Smad7. Conclusion Fibrotic hepatocyte exosomes may trigger HSCs activation through exosomal transfer in liver fibrosis. Exosomal miR-21-5p enhances HSCs activation, proliferation, and collagen synthesis by targeting Smad7, potentially serving as a diagnostic marker and therapeutic target for liver fibrosis.
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Project description:Gene expression analysis of stable HMGA2-overexpressing DLD-1 cells (DLD-1-HMGA2) and its control cells (DLD-1-Vector).
2019-08-29 | GSE136544 | GEO
Project description:Intervertebral disc (IVD) herniation is a complex and multifactorial condition with challenging diagnosis and limited therapeutic options, highlighting the need for reliable biomarkers to improve clinical decision-making. The aim of this study was to identify circulating prognostic biomarkers of IVD herniation regression. The plasma proteomic profile and the expression of circulating non-coding RNAs wereas analysed in a rat model ofs subjected to IVD herniation and proteomic and miRNA levels were correlated to herni-ation size. Four candidate proteins were identified (TNC, COPS3, JUP, GNAI2) that were significantly correlated with herniation size, with TNC further validated by ELISA. Additionally, miR-143-3p, miR-10b-5p, miR-27a-3p, miR-140-5p, miR-155-5p, miR-146a-5p and miR-21-5p were positively correlated with herniation size. Moreover, TNC, COPS3, JUP and GNAI2 were found to be potentiala targets of miR-155-5p. TNC-miR-155-5p pro-tein-miRNA pair standout as promising candidates to be part of a putative regulatory module worth investigating as a prognostic tool. This study provides the first combined proteomic and miRNAs account of preclinical plasma biomarkers of IVD herniation size, where TNC-miR-155-5p emerge as promising elements of a regulatory module with IVD herniation prognostic potential.
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Project description:Patients with advanced colorectal cancer (CRC) are commonly treated with systemic combination therapy but suffer eventually from drug resistance. MicroRNAs (miRNAs) are suggested to play a role in treatment resistance of CRC. We studied whether restoring downregulated miR-195-5p and 497-5p sensitize CRC cells to currently used chemotherapeutics 5-fluorouracil, oxaliplatin and irinotecan. Sensitivity to 5-FU, oxaliplatin and irinotecan before and after transfection with miR-195-5p and miR-497-5p mimics was analyzed in CRC cell lines HCT116, RKO, DLD-1 and SW480. Mass spectrometry based proteomic analysis of transfected and wild-type cells was used to identify targets involved in sensitivity to chemotherapy. Proteomic analysis revealed 181 proteins with significantly altered expression after transfection with miR-195-5p mimic in HCT116 and RKO, including 118 downregulated and 63 upregulated proteins. After transfection with miR-497-5p mimic, 130 proteins were significantly downregulated and 102 were upregulated in HCT116 and RKO (P<0.05 and FC<-3 or FC>3). CHUK and LUZP1 were coinciding downregulated proteins in sensitized CRC cells after transfection with either mimic. Resistance mechanisms of these two proteins may be related to nuclear factor kappa-B signaling and G1 cell cycle arrest, respectively. Restoring miR-195-5p and miR-497-5p expression enhanced sensitivity to chemotherapy, mainly oxaliplatin, in CRC cells and could be a promising treatment strategy for patients with mCRC. Proteomics revealed potential targets of these miRNAs involved in sensitivity to chemotherapy.
2019-09-27 | PXD015369 | Pride
Project description:Marked heterogeneity in radiosensitivity is a major challenge in the treatment of oral squamous cell carcinoma (OSCC), often resulting in poor outcomes for radioresistant tumors. The underlying molecular drivers of this resistance remain elusive. Here, we identify a novel mechanism in which miR-21-5p promotes radiation resistance by selectively activating the error-prone DNA double-strand break (DSB) repair pathway alternative end-joining (Alt-EJ). Integrative miRNA profiling, multi-omic analyses, and functional assays demonstrate that miR-21-5p upregulation coupled with suppression of its target gene signature increases Alt-EJ dependence for DSB repair. This Alt-EJ reliance enhances genomic instability, increases tumor mutational burden and microhomology-mediated indels, and confers pronounced radiation resistance in OSCC models, while correlating with poor radiotherapy response in patients. Importantly, pharmacological or genetic inhibition of Alt-EJ components, including PARP1 and POLQ, restores radiosensitivity in vitro and in vivo, with PARP1 inhibition specifically reversing miR-21-5p-mediated resistance in a syngeneic mouse model. Further RNA-seq analyses of these mice tumors confirmed that PARP inhibitor induced selective radiosensitization effects for miR-21-5p-overexpressing tumors were accompanied by a pronounced reduction in alt-EJ expression. Collectively, these findings establish the miR-21-5p/Alt-EJ axis as a key driver of radiation resistance in OSCC and support Alt-EJ targeting as a promising approach for precision radiosensitization.
2026-04-08 | GSE304277 | GEO
Project description:Marked heterogeneity in radiosensitivity is a major challenge in the treatment of oral squamous cell carcinoma (OSCC), often resulting in poor outcomes for radioresistant tumors. The underlying molecular drivers of this resistance remain elusive. Here, we identify a novel mechanism in which miR-21-5p promotes radiation resistance by selectively activating the error-prone DNA double-strand break (DSB) repair pathway alternative end-joining (Alt-EJ). Integrative miRNA profiling, multi-omic analyses, and functional assays demonstrate that miR-21-5p upregulation coupled with suppression of its target gene signature increases Alt-EJ dependence for DSB repair. This Alt-EJ reliance enhances genomic instability, increases tumor mutational burden and microhomology-mediated indels, and confers pronounced radiation resistance in OSCC models, while correlating with poor radiotherapy response in patients. Importantly, pharmacological or genetic inhibition of Alt-EJ components, including PARP1 and POLQ, restores radiosensitivity in vitro and in vivo, with PARP1 inhibition specifically reversing miR-21-5p-mediated resistance in a syngeneic mouse model. Further RNA-seq analyses of these mice tumors confirmed that PARP inhibitor induced selective radiosensitization effects for miR-21-5p-overexpressing tumors were accompanied by a pronounced reduction in alt-EJ expression. Collectively, these findings establish the miR-21-5p/Alt-EJ axis as a key driver of radiation resistance in OSCC and support Alt-EJ targeting as a promising approach for precision radiosensitization.
2026-04-08 | GSE304579 | GEO
Project description:Marked heterogeneity in radiosensitivity is a major challenge in the treatment of oral squamous cell carcinoma (OSCC), often resulting in poor outcomes for radioresistant tumors. The underlying molecular drivers of this resistance remain elusive. Here, we identify a novel mechanism in which miR-21-5p promotes radiation resistance by selectively activating the error-prone DNA double-strand break (DSB) repair pathway alternative end-joining (Alt-EJ). Integrative miRNA profiling, multi-omic analyses, and functional assays demonstrate that miR-21-5p upregulation coupled with suppression of its target gene signature increases Alt-EJ dependence for DSB repair. This Alt-EJ reliance enhances genomic instability, increases tumor mutational burden and microhomology-mediated indels, and confers pronounced radiation resistance in OSCC models, while correlating with poor radiotherapy response in patients. Importantly, pharmacological or genetic inhibition of Alt-EJ components, including PARP1 and POLQ, restores radiosensitivity in vitro and in vivo, with PARP1 inhibition specifically reversing miR-21-5p-mediated resistance in a syngeneic mouse model. Further RNA-seq analyses of these mice tumors confirmed that PARP inhibitor induced selective radiosensitization effects for miR-21-5p-overexpressing tumors were accompanied by a pronounced reduction in alt-EJ expression. Collectively, these findings establish the miR-21-5p/Alt-EJ axis as a key driver of radiation resistance in OSCC and support Alt-EJ targeting as a promising approach for precision radiosensitization.
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