Antagonizing miR-128 abrogates chemoresistance-associated metastasis and is therapeutic in non-small cell lung cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE67729 | GEO | 2015/04/10
SECONDARY ACCESSION(S): PRJNA280760
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-04-10 | E-GEOD-67729 | biostudies-arrayexpress
Project description:This experiment is designed to screen miRNAs that are deregulated during chemoresistance-associated metastasis of lung cancer cells. Chemoresistant metastatic in vivo tumor model of A549-luc-Vector cells was established after four rounds of cisplatin (CDDP) treatments compared to corresponding control solvent treatments. Upon examining profiles of miRNA expression differential between tumor-derived cultured cells from the Ctrl-4th and CDDP-4th treatments, most markedly upregulated and downregulated miRNAs in chemoresistant, metastatic A549-luc-CDDP-4th cells were identified. In order to establish a chemoresistant in vivo tumor model, after inoculation of A549-luc-Vector cells, cisplatin (CDDP) or control solvent was intraperitoneally (i.p.) injected six rounds in a two-week period and cells were isolated from corresponding resultant tumors, cultured and re-transplanted into syngeneic mice to receive the next round of treatment. In our experimental model, human lung cancer xenografts developed chemoresistance in the third round of CDDP treatment (CDDP-3rd) and chemoresistance-associated metastases following the fourth round of treatment. Tumor-derived cultured cells from Ctrl-4th and CDDP (cisplatin)-4th treatment were subjected to miRNA array (Agilent-031181 human miRNA (8*60k) V16.0) analysis, with two biological replications for each treatment.
2015-04-10 | E-GEOD-67727 | biostudies-arrayexpress
Project description:This experiment is designed to evaluate gene expression alteration and significant pathway(s) following miR-128 transduction in A549 lung cancer cells. We find several significant pathways, including the Wnt/β-catenin signaling and TGF-β signaling activated by miR-128 overexpression. Total RNA were extracted from A549 lung cancer cells stably transduced with miR-128 precursor or vector control and subjected to mRNA microarray (Agilent-014850 Whole Human Genome Microarray 4x44K) analysis, with two biological replications for each treatment.
2015-04-10 | E-GEOD-67728 | biostudies-arrayexpress
Project description:This experiment is designed to evaluate gene expression alteration and significant pathway(s) following miR-128 transduction in A549 lung cancer cells. We find several significant pathways, including the Wnt/β-catenin signaling and TGF-β signaling activated by miR-128 overexpression.
2015-04-10 | GSE67728 | GEO
Project description:This experiment is designed to screen miRNAs that are deregulated during chemoresistance-associated metastasis of lung cancer cells. Chemoresistant metastatic in vivo tumor model of A549-luc-Vector cells was established after four rounds of cisplatin (CDDP) treatments compared to corresponding control solvent treatments. Upon examining profiles of miRNA expression differential between tumor-derived cultured cells from the Ctrl-4th and CDDP-4th treatments, most markedly upregulated and downregulated miRNAs in chemoresistant, metastatic A549-luc-CDDP-4th cells were identified.
2015-04-10 | GSE67727 | GEO
Project description:Antagonizing miR-128 abrogates chemoresistance-associated metastasis and is therapeutic in non-small cell lung cancer
| PRJNA280760 | ENA
Project description:Cisplatin is effective as a single agent or in combination with other drugs for the treatment of non-small cell lung cancer (NSCLC). A concerning clinical challenge with cisplatin-based NSCLC chemotherapy is the intrinsic and acquired chemoresistance to cisplatin. The sterile ? motif domain-containing (SAMD9) gene has been reported as a potent tumor suppressor gene that inhibits tumorigenesis and progression of NSCLC. microRNAs (miRNA) have been revealed to play important roles in the regulation of cancer chemoresistance. To the best of our knowledge the present study explored the role of miRNA/SAMD9 signaling in regulating cisplatin chemoresistance in NSCLC for the first time. Out of the several candidate miRNAs predicted to bind the 3'-untranslated region (UTR) of the SAMD9 gene, miRNA-96 (miR-96) demonstrated significant target-sequence-specific inhibition of the SAMD9 3'-UTR luciferase reporter activity in NSCLC cells. In addition, while NSCLC tumor samples exhibited significantly higher expression levels of miR-96 compared with adjacent normal tissues, the expression levels of SAMD9 were significantly lower than those in adjacent normal tissues. miR-96 and SAMD9 were overexpressed and knocked down in the human NSCLC H358 and H23 cell lines and the half maximal inhibitory concentration (IC50) of cisplatin and cell apoptosis rate under cisplatin treatment were used as measures of cisplatin chemoresistance. The present results identified that overexpression of miR-96 in NSCLC cells markedly decreased SAMD9 expression and cisplatin-induced apoptosis, and increased the cisplatin IC50, which could be eliminated by overexpression of SAMD9. By contrast, knocking down miR-96 in NSCLC cells using antagomir-96 significantly increased SAMD9 expression and the cisplatin-induced apoptosis and decreased cisplatin IC50, which could be completely reversed by a knockdown of SAMD9. In conclusion, the current study demonstrates that miR-96 targets and downregulates SAMD9 in NSCLC, which decreases cisplatin-induced apoptosis and induces cisplatin chemoresistance in NSCLC cells. The findings of the present study add novel insights into the function of miR-96 and SAMD9 in cancer, as well as into the molecular mechanisms underlying NSCLC chemoresistance.
| S-EPMC4734049 | biostudies-literature
Project description:Cancer chemoresistance and metastasis are tightly associated features. However, whether they share common molecular mechanisms and thus can be targeted with one common strategy remain unclear in non-small cell lung cancer (NSCLC). Here, we report that high levels of microRNA-128-3p (miR-128-3p) is key to concomitant development of chemoresistance and metastasis in residual NSCLC cells having survived repeated chemotherapy and correlates with chemoresistance, aggressiveness and poor prognosis in NSCLC patients. Mechanistically, miR-128-3p induces mesenchymal and stemness-like properties through downregulating multiple inhibitors of Wnt/β-catenin and TGF-β pathways, leading to their overactivation. Importantly, antagonism of miR-128-3p potently reverses metastasis and chemoresistance of highly malignant NSCLC cells, which could be completely reversed by restoring Wnt/β-catenin and TGF-β activities. Notably, correlations among miR-128-3p levels, activated β-catenin and TGF-β signalling, and pro-epithelial-to-mesenchymal transition/pro-metastatic protein levels are validated in NSCLC patient specimens. These findings suggest that miR-128-3p might be a potential target against both metastasis and chemoresistance in NSCLC.
| S-EPMC5481840 | biostudies-literature
Project description:ObjectNon-small lung cancer (NSCLC), with a poor 5-year survival rate (16%), is the major type of lung cancer. Metastasis has been identified as the main factor that leads to NSCLC therapy failure. MiR-206 is a metastasis suppressor in many cancers, including colorectal cancer, renal cell carcinoma and breast cancer. However, the role of miR-206 in NSCLC metastasis and the underlying mechanism are still obscure.MethodsQuantitative reverse-transcription PCR (q-RT-PCR) assay was used to detect miR-206 mRNA of NSCLC tissues and lung cancer lines. The MTT assay, scratch wound healing assay, transwell migration assay and transwell invasion assay were conducted to illuminate the effect of miR-206 on A549 cells' proliferation, migration and invasion. Gaussia luciferase reporter assay, q-RT-PCR and western blotting assay were used to explore the underlying mechanism. Also, the A549 xenograft model was conducted to evaluate the anti-tumor effect of miR-206 in vivo.ResultsThe results showed that miR-206 expression was decreased in NSCLC tissues and lung cancer cells. Further research demonstrated that miR-206 inhibited the proliferation, migration and invasion of A549 cells via negatively regulating Coronin-1C (CORO1C), and CORO1C deletion significantly rescues the miR-206 mediated inhibitory effect on A549 cells. Moreover, miR-206 exhibited a perfect anti-tumor effect in the A549 xenograft model.ConclusionOur study reveals that miR-206 functions as a tumor metastasis suppressor and sheds new light on the clinical significance of miR-206 in NSCLC therapy.
| S-EPMC7079403 | biostudies-literature
Project description:Dysregulated microRNAs (miRNAs) play an important role in osteosarcoma (OS) progression. In the present study, we investigate the clinical significance of serum miR-491 level and the potential role of miR-491 in OS lung metastasis and chemoresistance. Clinical data show that the level of miR-491 was decreased in serum from OS patients compared with healthy control subjects, and that a decreased serum miR-491 level is correlated with increased metastasis, poor chemoresponse, and lower survival rate in OS patients. In vitro and in vivo experiments show that overexpression of miR-491 suppresses OS cell lung metastasis, whereas it enhances cisplatin (CDDP)-induced tumor growth inhibition and apoptosis. In contrast, inhibition of miR-491 stimulates OS cell lung metastasis and suppresses CDDP-induced tumor growth inhibition and apoptosis. Furthermore, we demonstrate that miR-491 exerts its role by directly targeting αB-crystallin (CRYAB) in OS. Our findings suggest that serum level of miR-491 has potential as a biomarker for predicting OS progression and prognosis of OS patients. Additionally, restoration of miR-491 may be a novel strategy for inhibiting OS lung metastasis and overcoming OS cell resistance to chemotherapy.
| S-EPMC5589150 | biostudies-literature