BEX3 contributes to cisplatin chemoresistance in nasopharyngeal carcinoma

Autor: Wei Gao, Chiao-Yun Chu, Jimmy Yu Wai Chan, Siqi Chen, Thian-Sze Wong, John Zeng Hong Li
Rok vydání: 2016
Předmět:
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
Population
cisplatin
Biology
OCT4
Small hairpin RNA
03 medical and health sciences
Mice
0302 clinical medicine
Cancer stem cell
Internal medicine
Cell Line
Tumor
BEX3
medicine
otorhinolaryngologic diseases
Animals
Humans
Radiology
Nuclear Medicine and imaging
education
Original Research
Cancer Biology
Cisplatin
education.field_of_study
Gene knockdown
Nasopharyngeal Carcinoma
Carcinoma
Nasopharyngeal Neoplasms
medicine.disease
Up-Regulation
Gene Expression Regulation
Neoplastic
stomatognathic diseases
030104 developmental biology
Nasopharyngeal carcinoma
Drug Resistance
Neoplasm
030220 oncology & carcinogenesis
Cancer research
Acquired resistance
Stem cell
Signal transduction
Apoptosis Regulatory Proteins
Octamer Transcription Factor-3
medicine.drug
Zdroj: Cancer Medicine
ISSN: 2045-7634
Popis: Nasopharyngeal carcinoma (NPC) can develop cisplatin‐resistant phenotype. Research has revealed that enriched in cancer stem cell population is involved in developing cisplatin‐resistant phenotype. CD271 is a candidate stem cell maker in head and neck cancers. The CD receptor does not possess any enzymatic property. Signal transduction function of CD271 is mediated by the cellular receptor‐associated protein. Our data showed that Brain‐expressed X‐linked 3 (BEX3), a CD271 receptor‐associated protein, was overexpressed in NPC. BEX3 overexpression was a unique event in cancer developed in the head and neck regions, especially NPC. BEX3 expression was inducible by cisplatin in NPC. In cisplatin‐resistant NPC xenograft, treatment with nontoxic level of cisplatin led to a remarkable increase in BEX3 level. High BEX3 expression was accompanied with high octamer‐binding transcription factor 4 (OCT4) expression in cisplatin‐resistant NPC. To confirm the inducing role of BEX3 on OCT4 expression, we knockdown BEX3 using siRNA and compared the expression of OCT4 with mock transfectants. Suppressing BEX3 transcripts led to a significant reduction in OCT4. In addition, targeting BEX3 using shRNA could increase the sensitivity of NPC cells to cisplatin. In summary, our results indicated a unique functional role of BEX3 in mediating the sensitivity of NPC cells to cisplatin. Targeting or blocking BEX3 activity might be useful in reversing the cisplatin‐resistant phenotype in NPC.
Databáze: OpenAIRE
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