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Therapeutic potential for reversing miR-634-mediated cytoprotective processes to improve the efficacy of chemotherapy against oral squamous cell carcinoma

ABSTRACT: For advanced oral squamous cell carcinoma (OSCC), increasing sensitivity to chemotherapy is a major challenge in improving treatment outcomes, and targeting cytoprotective processes that lead to the chemotherapy resistance of cancer cells may be therapeutically promising. Tumor-suppressive microRNAs (miRs) can target multiple cancer-promoting genes concurrently, and are thus expected to be useful seeds for cancer therapeutics. We revealed that miR-634-meditated targeting of multiple cytoprotective process-related genes, including cellular inhibitor of apoptosis proteins 1 (cIAP1), can effectively increase cisplatin (CDDP)-induced cytotoxicity and overcome CDDP resistance in OSCC cells. The combination of topical treatment with miR-634 ointment and administration of CDDP was synergistically effective against OSCC-tumor growth in a xenograft mouse model. Furthermore, the expression of miR-634 target genes is frequently upregulated in primary OSCC tumors. Our study suggests that reversing miR-634-mediated cytoprotective processes activated in cancer cells is a potentially useful strategy to improve CDDP efficacy against advanced OSCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE194269 | GEO | 2022/05/25

REPOSITORIES: GEO

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Improving the efficacy of EGFR inhibitors by topical treatment of cutaneous squamous cell carcinoma with miR-634 ointment

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2020-12-15 | GSE159093 | GEO

miR-634 restores drug sensitivity in resistant ovarian cancer cells by targeting the Ras-MAPK pathway

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2014-02-04 | GSE54665 | GEO

miR-634 restores drug sensitivity in resistant ovarian cancer cells by targeting the Ras-MAPK pathway

2014-02-04 | E-GEOD-54665 | biostudies-arrayexpress

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Project description:We have extended our investigation to advanced-stage NSCLC by analyzing gene expression in peripheral blood mononuclear cells (PBMC) from patients with newly-diagnosed NSCLC and histopathology of either AC or SCC. Furthermore, to establish a direct link between gene expression and chemotherapy treatment, PBMC from patients who have received 4 courses of combination chemotherapy with CDDP and GEM were obtained, and the effects of chemotherapy on global gene expression were evaluated using microarray analyses. We analyzed microarray gene expression profiles of peripheral blood mononuclear cells from 30 patients with newly-diagnosed advanced stage NSCLC, and 20 age, sex, and co-morbidity-matched healthy controls (HC). All the cancer patients received a maximum of six courses of chemotherapy with cisplatin and gemcitabine of a 28-day cycle as first line treatment.Furthermore, to establish a direct link between gene expression and chemotherapy treatment, PBMC from patients who have received 4 courses of combination chemotherapy with CDDP and GEM were obtained, and the effects of chemotherapy on global gene expression were evaluated using microarray analyses.

2012-07-31 | E-GEOD-39345 | biostudies-arrayexpress

Microarray gene expression profiles of peripheral blood mononuclear cells in patients with advanced stage non-small cell lung cancer treated with first line combination chemotherapy with or without Rikkunshito treatment

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2018-05-31 | GSE103250 | GEO

Genes regulated by hepatocyte growth factor as targets to sensitize ovarian cancer cells to cisplatin

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2009-06-10 | GSE16424 | GEO

Expression profiling of cisplatin resistant cells derived from H460 lung cell line.

Project description:Combination of platinum-based chemotherapy and radiation is currently the standard treatment for locally advanced lung cancer patients. However, therapeutic resistance to these therapies may arise from the presence of cancer stem cells (CSCs). To investigate the CSCs hypothesis of chemo-radiation resistance, we used microarray assay to profile CSCs-like cisplatin-resistant lung cancer cells (CDDP-R) versus its parental cells. CDDP-R cells were established by exposing H460 lung cancer cells to 3¬µM cisplatin for 7 days, followed by 0.8% methylcellulose selection over 14 consecutive days.¬†We found that CDDP-R cells expressed higher levels of stem cell markers, including CD133 and ALDH. They are more resistant to cisplatin- and etoposide-induced apoptosis and to high radiation dose (20Gy). Clonogenic assays suggest that CDDP-R cells were more resistant to radiation than parental H460 cells (DER=1.21, p<0.01). Xenograft studies suggest that CDDP-R cells were more tumorigenic (p<0.001). Microarray and comprehensive protein interaction networks analyses revealed IGFBP3 as a highly ranked hub protein which plays an important role in the mechanism of cisplatin resistance. We found reduced level of IGFBP3 and enhanced IGFR-1 activation upon IGF stimulation in CDDP-R cells. The specific targeting of IGF-1R using siRNA resulted in significant sensitization of CDDP-cells (DER=1.17, p<0.05) to radiation compared with the parental H460 cells. Our findings suggest that CDDP-R cells have the characteristics of CSCs and constitute a ‚Äúsuitable‚Äù model to study lung CSCs. Profiling of CSCs-like H460 cells led to the identification of IGF as an important pathway for chemo- and radiotherapy resistance in lung cancer. gene expression comparison of two groups

2011-09-26 | E-GEOD-21656 | biostudies-arrayexpress

Proteome dynamics during cisplatin exposure in sensitive and resistant human lung cancer cells

Project description:Lung cancer is the leading cause of cancer-related deaths and its treatment is based in chemotherapy using platinum containing compounds, mainly cisplatin (CDDP). Many patients show resistance to CDDP leading to treatment failure. To understand the mechanisms involved in CDDP resistance in lung cancer, we used CDDP-sensitive (A549) and –resistant (A549/CDDP) cells to identify newly synthesized proteins in response to CDDP treatment using BONCAT technique. In addition the steady-state proteome of A549 and A549/CDDP cells was also evaluated. It was identified 70 and 69 proteins upregulated by CDDP in A549 and A549/CDDP cells, respectively. The set of proteins upregulated by CDDP in both cells are associated to GO terms related to proteostasis, telomere maintenance cell, RNA processing, cytoskeleton and response to oxidative stress. Interestingly, the profile of biological processes enriched in A549 cells after CDDP treatment is very similar to those identified in the steady-state proteome of A549/CDDP cells, suggesting their positive selection in CDDP-resistant cells development. Therefore, this study of proteomic response to CDDP is relevant to the identification of potential protein targets to development of therapeutic strategies to block drug resistance pathways.

2023-03-10 | PXD021779 | Pride

A three–microRNA signature as a potential biomarker for the early detection of oral cancer

Project description:Background: Oral squamous cell carcinoma (OSCC) is often diagnosed at a late stage and may be malignantly transformed from oral leukoplakia (OL). This study aimed to identify potential plasma microRNAs (miRNAs) for the early detection of oral cancer. Methods: Plasma from normal, OL, and OSCC patients were evaluated. Small RNA sequencing was used to screen differently expressed miRNAs among the groups. Next, these miRNAs were validated with individual samples by quantitative real-time polymerase chain reaction (qRT-PCR) assays. The possible physiological roles of the identified miRNAs were further investigated using bioinformatics analysis. Results: Three miRNAs (miR-222-3p, miR-150-5p, and miR-423-5p) were identified as differentially expressed among groups; miR-222-3p and miR-423-5p negatively correlated with T stage, lymph node metastasis status, and clinical stage. A high diagnostic accuracy (Area under curve = 0.88) was demonstrated for discriminating OL from OSCC. Bioinformatics analysis reveals that miR-423-5p and miR-222-3p are significantly over-expressed in oral cancer tissues and involved in various cancer pathways. Conclusions: The three plasma miRNA panel may be useful to monitor malignant progression from OL to OSCC and as potential biomarkers for early detection of oral cancer.

2018-04-17 | GSE104440 | GEO

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