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Oncotarget Exosome mediated miR-155 delivery confers cisplatin chemoresistance in oral cancer cells via epithelial-mesenchymal transition


FOR IMMEDIATE RELEASE
2020-04-13

Oncotarget Volume 11 Issue 13 reported that in the present study, we document for the first time the critical role of exosomes in mediating increments in mi R-155 expression in OSCC cells that have acquired cisplatin resistance.

Importantly, exosomal transfer from cis Res to the cisplatin sensitive cells was found to confer significant mi R-155 induction in the recipient cis Sens cells.

Restoration of mi R-155 expression in cis Sens cells following mi R-155 mimics treatment led to epithelial to mesenchymal transition, enhancements in their migratory potential as well as acquisition of resistant phenotype.

Dr. Kiran Kalia, Dr. Rachana Garg, and Dr. Alok Jain from the Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Ahmedabad, Gujarat, India said, "Oral squamous cell carcinoma (OSCC) ranks sixth amongst all cancers worldwide, and one of the most predominant and leading cancers found in Indian subcontinent."

"Oral squamous cell carcinoma (OSCC) ranks sixth amongst all cancers worldwide, and one of the most predominant and leading cancers found in Indian subcontinent."

- Dr. Kiran Kalia, Dr. Rachana Garg, and Dr. Alok Jain, Department of Biotechnology, National Institute of Pharmaceutical Education and Research

Oral squamous cell carcinoma ranks sixth amongst all cancers worldwide, and one of the most predominant and leading cancers found in Indian subcontinent.

Expression patterns of exosomal-derived mi RNAs differ greatly between cancer and normal control cells, thereby hinting at the role of exosomal mi RNAs as potential biomarkers for cancer diagnosis, including OSCC. In contrast, mi R-21 was found to be overexpressed in multiple cancers and its overexpression mediated cisplatin resistance particularly, in ovarian cancer via PTEN down-regulation.

In the present study, the authors demonstrate for the first time that mi R-155 is overexpressed in cisplatin resistant vs cis-senstive oral cancer cells.

Figure 1: (A) miR-155 expression in clinical samples was quantified by q-PCR and normalized with respect to U6 as housekeeping gene. miR-155 expression profiling in cisRes and cisSens oral cancer cells at the (B) cellular and (C) exosomal level. (D and E) Western blot analysis for the exosomal marker CD-9 in exosomes isolated from serum of clinical samples and cisRes and cisSens SCC-131 oral cancer cells. In the absence of a well-accepted standard internal control, densitometric analysis was done by normalizing the CD9 blot with a prominent band visualized on the PVDF membrane following Ponceau-S staining. Data are expressed as mean +/– SD.*p < 0.05 and **p < 0.01 compared with the cisSens cells or healthy controls in case of clinical samples. (n = 3). Two independent experiments gave similar results.

In consonance to this, mi R-155 upregulation was observed in oral cancer patients with disease recurrence following cisplatin treatment compared to the healthy controls or tobacco smokers with no cancer history.

The Kalia/Garg/Jain Research Team concluded in their Oncotarget Research Article, "Taken together, our results provide mechanism of transmission of cisplatin-resistance in oral cancer via exosomal miR-155 and identifies the relevance of its target FOXO3a in mediating chemoresistance. Thus, miR-155 targeting therapies when combined with conventional chemotherapy might be helpful to combat chemoresistance."

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DOI - https://doi.org/10.18632/oncotarget.27531

Full text - https://www.oncotarget.com/article/27531/text/

Correspondence to - Kiran Kalia - director@niperahm.ac.in, Rachana Garg - rachanag@niperahm.ac.in, and Alok Jain - alokjain@niperahm.ac.in

Keywords - cisplatin chemoresistance, miRNA155, exosomes, oral cancer, apoptosis

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