Exosomes containing miR-21 transfer the characteristic of cisplatin resistance by targeting PTEN and PDCD4 in oral squamous cell carcinoma.

Resistance to chemotherapy remains a major obstacle for the effective treatment of oral squamous cell carcinoma (OSCC). Evidence for the involvement of exosomes as important regulators of cisplatin chemoresistance in OSCC is still poorly understood. Our objective of this study was to explore the roles for exosomes in modulating key cellular pathways mediating response to chemotherapy. We first developed the cisplatin-resistant cell lines (HSC-3-R and SCC-9-R) and found that the conditioned media from cisplatin-resistant OSCC cells enhanced the chemoresistance of parental OSCC cell. The release of exosomes was blocked by inhibitor (GW4869) and exosomes were found to be involved in the chemoresistance of parental OSCC cell transferred from resistant cells. The exosomes derived from resistant cells and parental cells were isolated. Then, the isolated exosomes were characterized and quantified by electron microscopy, qNano analysis, and western blot analysis. Exosomes derived from cisplatin-resistant OSCC cells were found to enhance the chemoresistance of OSCC cell and decrease the DNA damage signaling in response to cisplatin. It was also found that exosomes derived from cisplatin-resistant OSCC cells transferred miR-21 to OSCC parental cells and induced cisplatin resistance by targeting phosphatase and tensin homolog and programmed cell death 4. Furthermore, the roles of cisplatin-resistant OSCC cells-derived exosomes in vivo were confirmed by subcutaneous xenograft mouse model. Collectively, the results suggest that exosomes released from cisplatin-resistant OSCC cells transmit miR-21 to induce cisplatin resistance of OSCC cells.

Liu T ，Chen G ，Sun D ，Lei M ，Li Y ，Zhou C ，Li X ，Xue W ，Wang H ，Liu C ，Xu J ... -  《-》

LncRNA UCA1 promotes proliferation and cisplatin resistance of oral squamous cell carcinoma by sunppressing miR-184 expression.

Chemotherapy resistance has become the main obstacle for the effective treatment of human cancers. Long non-coding RNA urothelial cancer associated 1 (UCA1) is generally regarded as an oncogene in some cancers. However, the function and molecular mechanism of UCA1 implicated in cisplatin (CDDP) chemoresistance of oral squamous cell carcinoma (OSCC) is still not fully established. UCA1 expression in tumor tissues and cells was tested by qRT-PCR. MTT, flow cytometry and caspase-3 activity analysis were explored to evaluate the CDDP sensitivity in OSCC cells. Western blot analysis was used to measure BCL2, Bax and SF1 protein expression. Luciferase reporter assay was conducted to investigate the molecular relationship between UCA1, miR-184, and SF1. Nude mice model was used to confirm the functional role of UCA1 in CDDP resistance in vivo. UCA1 expression was upregulated in OSCC tissues, cell lines, and CDDP resistant OSCC cells. Function analysis revealed that UCA1 facilitated proliferation, enhanced CDDP chemoresistance, and suppressed apoptosis in OSCC cells. Mechanisms investigation indicated that UCA1 could interact with miR-184 to repress its expression. Rescue experiments suggested that downregulation of miR-184 partly reversed the tumor suppression effect and CDDP chemosensitivity of UCA1 knockdown in CDDP-resistant OSCC cells. Moreover, UCA1 could perform as a miR-184 sponge to modulate SF1 expression. The OSCC nude mice model experiments demonstrated that depletion of UCA1 further boosted CDDP-mediated repression effect on tumor growth. UCA1 accelerated proliferation, increased CDDP chemoresistance and restrained apoptosis partly through modulating SF1 via sponging miR-184 in OSCC cells, suggesting that targeting UCA1 may be a potential therapeutic strategy for OSCC patients.

Fang Z ，Zhao J ，Xie W ，Sun Q ，Wang H ，Qiao B ... -  《Cancer Medicine》

LncRNA HOXA11-AS Promotes Proliferation and Cisplatin Resistance of Oral Squamous Cell Carcinoma by Suppression of miR-214-3p Expression.

Wang X ，Li H ，Shi J 《-》

WP1066 sensitizes oral squamous cell carcinoma cells to cisplatin by targeting STAT3/miR-21 axis.

Zhou X ，Ren Y ，Liu A ，Jin R ，Jiang Q ，Huang Y ，Kong L ，Wang X ，Zhang L ... -  《Scientific Reports》

Oral squamous cell carcinoma-derived exosomes promote M2 subtype macrophage polarization mediated by exosome-enclosed miR-29a-3p.

Cai J ，Qiao B ，Gao N ，Lin N ，He W ... -  《-》