Functional characterization of TRPM7 in nasopharyngeal carcinoma and its knockdown effects on tumorigenesis
- 164 Downloads
The aim of this study was to evaluate the association of functional expression of TRPM7 with nasopharyngeal carcinoma (NPC) growth. We examined the correlation of TRPM7 expression with cell growth and proliferation, cell cycle, and apoptosis in vitro in NPC cell lines and NPC tumorigenesis in mice by conducting experiments in mice and by further analyzing the tumor volume and growth. We further explored to see whether there is any positive correlation with the TRPM7 knockdown in NPC cells with their sensitivity to radiation. We found that the functional expression of TRPM7 in nasopharyngeal carcinoma is a critical requirement for physiological processes such as cell cycle, resistance to apoptosis, and cell proliferation. TRPM7 knockdown also enhanced sensitivity to radiotherapy of nasopharyngeal carcinoma. Moreover, we identified TRPM7 as a novel potential regulator of cell proliferation in NPC, through signal transducer and activator of transcription 3 (STAT3)-mediated signaling pathway and other anti-apoptotic factors. TRPM7 and STAT3 activation might be critical for the growth of NPC cells and could be an effective target for treatment of nasopharyngeal carcinoma.
KeywordsNasopharyngeal carcinoma TRPM7 Prognosis Apoptosis CNE-1 cells STAT3 Radiotherapy
This study was supported by the Natural Science Foundation of Guangdong Province, China (S2013040014989) and China Postdoctoral Science Foundation (2015M570742).
XX. W and BQ. L conceived and designed the study and critically revised the manuscript.
Y. Q, ZW. L, and JY. L performed the experiments, analyzed the data, and drafted the manuscript.
WZ. W, AS. L, and PX. S helped in study design, study implementation, and manuscript revision.
All authors read and approved the final manuscript.
Compliance with ethical standards
Conflicts of interest
- 6.Chow E, Payne D, Keane T, Panzarella T, Izard MA. Enhanced control by radiotherapy of cervical lymph node metastases arising from nasopharyngeal carcinoma compared with nodal metastases from other head and neck squamous cell carcinomas. Int J Radiat Oncol Biol Phys. 1997;39:149–54.CrossRefPubMedGoogle Scholar
- 24.Rybarczyk P, Gautier M, Hague F, Dhennin-Duthille I, Chatelain D, Kerr-Conte J, et al. Transient receptor potential melastatin-related 7 channel is overexpressed in human pancreatic ductal adenocarcinomas and regulates human pancreatic cancer cell migration. Int J Cancer. 2012;131:E851–61.CrossRefPubMedGoogle Scholar
- 61.Oudejans JJ, Harijadi H, Kummer JA, Tan IB, Bloemena E, Middeldorp JM, et al. High numbers of granzyme b/cd8-positive tumour-infiltrating lymphocytes in nasopharyngeal carcinoma biopsies predict rapid fatal outcome in patients treated with curative intent. J Pathol. 2002;198:468–75.CrossRefPubMedGoogle Scholar
- 70.Li H, Liu A, Zhao Z, Xu Y, Lin J, Jou D, et al. Fragment-based drug design and drug repositioning using multiple ligand simultaneous docking (mlsd): identifying celecoxib and template compounds as novel inhibitors of signal transducer and activator of transcription 3 (stat3). J Med Chem. 2011;54:5592–6.CrossRefPubMedPubMedCentralGoogle Scholar