Abstract
Our previous microarray analysis indicated that miR-34c was downregulated in nasopharyngeal carcinoma (NPC). However, little is known about the function and molecular mechanism of miR-34c in NPC. In this study, miR-34c was found to be significantly downregulated in NPC cell lines and clinical tissues. Ectopic expression of miR-34c suppressed NPC cell viability, colony formation, anchorage-independent growth, cell migration and invasion in vitro, and inhibited xenograft tumor growth and lung metastasis in vivo. MET proto-oncogene (MET) was identified as a direct target of miR-34c using luciferase reporter assays, quantitative RT-PCR, western blotting and immunofluorescent staining. Overexpression of miR-34c markedly reduced MET expression at both the mRNA and protein levels. Knockdown of MET suppressed NPC cell proliferation, migration and invasion, whereas the restoration of MET rescued the suppressive effects of miR-34c. The demethylation agent 5-aza-2′-deoxycytidine (DAC) restored the expression of miR-34c in NPC cell lines. The promoter region of miR-34c was hypermethylated in NPC cells. In conclusion, miR-34c suppresses tumor growth and metastasis in NPC by targeting MET. The newly identified miR-34c/MET pathway provides further insights into the development and progression of NPC, and may represent a novel therapeutic target for NPC treatment.
Highlights
NPC is observed in Southern China, where the rates vary from 20 to 50 cases per 100 000 people.[1,2] local and regional control have improved owing to the application of intensity-modulated radiotherapy and chemoradiotherapy, the prognosis for patients with NPC still remains very poor because of recurrence and distant metastasis.[3]
Several miRNAs have been identified to be dysregulated and affect cell growth, proliferation and metastasis in NPC, including miR-451, miR-29c, miR-26a and miR-9.18–21 These findings indicate that miRNAs have important roles in nasopharyngeal tumorigenesis
We found that miR-34c was downregulated and could suppress tumor growth and metastasis in NPC
Summary
NPC is observed in Southern China, where the rates vary from 20 to 50 cases per 100 000 people.[1,2] local and regional control have improved owing to the application of intensity-modulated radiotherapy and chemoradiotherapy, the prognosis for patients with NPC still remains very poor because of recurrence and distant metastasis.[3] understanding the molecular mechanisms that underlie the initiation and progression of NPC is of crucial significance to the development of novel therapeutic strategies. Further knowledge of the functional effects and molecular mechanisms of miRNAs may help to elucidate the biological events regulating the development and progression of NPC. The newly identified miR-34c/MET pathway expands our understanding of the mechanisms underlying the development and progression of NPC, and may provide a novel therapeutic target for the treatment of NPC
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
