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 《-》

LncRNA XIST promotes proliferation and cisplatin resistance of oral squamous cell carcinoma by downregulating miR-27b-3p.

Chemotherapy resistance has become a major obstacle to effective treatment of human cancer. This study aimed to investigate the effect of lncRNA XIST on cell proliferation and cisplatin (CDDP) of oral squamous cell carcinoma (OSCC). RT-qPCR and Western blot analysis were used to detect mRNA and protein expression. CCK-8 and flow cytometry assays were explored to evaluate CDDP sensitivity in OSCC cells. The relationship between lncRNA XIST and miR-27b-3p was confirmed by luciferase reporter assay. The results showed that lncRNA XIST was upregulated in OSCC tissues, cell lines, and CDDP-resistant OSCC cells. Functionally, upregulation of lncRNA XIST promoted cell proliferation, enhanced CDDP resistance, and inhibited apoptosis in OSCC cells. In addition, lncRNA XIST acts as a molecular sponge for miR-27b-3p in OSCC. Downregulation of miR-27b-3p partially reversed the tumor suppression effect and CDDP chemosensitivity of XIST knockdown in CDDP-resistant OSCC cells. In conclusion, lncRNA XIST promotes cell proliferation and enhances resistance to CDDP in OSCC by downregulating miR-27b-3p.

Ma SQ ，Wang YC ，Li Y ，Li XY ，Yang J ，Sheng YM ... -  《JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS》

Long noncoding RNA UCA1 promotes cell growth, migration, and invasion by targeting miR-143-3p in oral squamous cell carcinoma.

The long noncoding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) is dysregulated in many types of tumors; however, its role in oral squamous cell carcinoma (OSCC) remains unclear. This study aims to determine the effect of lncRNA UCA1 on OSCC. Fifty-six paired OSCC and adjacent nontumorous tissues were collected and the levels of UCA1, miR-143-3p, and MYO6 in the tissues were evaluated by qRT-PCR. In in vitro experiments, cell viability, migration, and invasion were measured by, respectively, performing CCK-8, wound healing, and transwell assays. The target relationships among UCA1, miR-143-3p, and MYO6 were verified by dual-luciferase assay. Western blot and immunohistochemistry were carried out to determine the protein levels. Xenograft mouse model was established to explore the effects of UCA1 in vivo. Levels of UCA1 and MYO6 were increased significantly in OSCC, while the level of miR-143-3p was decreased compared with the adjacent nontumorous tissues. UCA1 promoted OSCC cell growth, migration, and invasion both in vitro and in vivo, while miR-143-3p reversed the progression. MYO6 was validated as a target for miR-143-3p, and MYO6 overexpression reversed the effects of miR-143-3p mimic on OSCC cells. LncRNA UCA1 contributes to the proliferation and metastasis of OSCC cells by targeting miR-143-3p and upregulating its downstream gene MYO6. UCA1 could serve as a promising novel target therapy for treatment of OSCC.

Duan Q ，Xu M ，Wu M ，Zhang X ，Gan M ，Jiang H ... -  《Cancer Medicine》

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 ... -  《-》