Disregulation of miR-143/145 and miR-363 in head and neck cancers

• 作 者: Qiang Sun Jianjun Zhang Qin Xu Wantao Chen
• 机 构: Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200011
• 出 处: 2014第八次全国口腔颌面-头颈肿瘤学术研讨会
• 发表日期: 2014年3期
• 关键词: microRNA miR-143/145 miR-363 head and neck cancer

　　Objective:Dysregulated microRNAs(miRNAs)play an important role in many malignant tumors.However,elucidating the roles of miRNAs in cancer biology,especially in head and neck epithelial cancers,remains an ongoing process,such as carcinogenesis,invasion and metastasis.Methods and materials:MiRNA array screening and real-time reverse transcription-PCR were performed to identify the differential expression of miRNAs involved in different phenotype cell lines and cancer tissues.MiRNAs expressions were validated in mentioned samples by real-time PCR.To assess the biological significance of miRNAs were over-expressed or down-expressed in cells followed by in vitro and in vivo functional assays.MiRNAs direct targets were identified through the TargetScan database and dual luciferase reporter assays and confirmed.Results:Our results showed that both miR-143 and miR-145 can negatively modulate expression of their target gene,MDM2.The miR-143/145 is post-transcriptionally activated by up-regulated p53,thereby generating a short miRNAs-MDM2-p53 feedback loop.Re-expression of these miRNAs suppresses cellular growth and triggers the apoptosis of epithelial cancer,in vitro and in vivo,by enhancing p53 activity via MDM2 turnover.The study also confirmed that miR-363 is down-regulated in HNSCC tissues with lymph node metastasis and cell lines with highly invasive capacity.We found that podoplanin(PDPN)is up-regulated in the metastatic HNSCC tissues,and ectopic over-expression of miR-363 suppressed the metastatic behaviour of HNSCC cells by directly targeting PDPN.Conclusions:These findings suggest that some miRNAs,such as niR-143/145 and miR-363 are expressed abnormally.Re-expression of miR-143 and miR-145 may be a reasonable strategy for treatment of epithelial cancers.MiR-363 can provide insights into the therapeutic value in reducing cancer metastasis.