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Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Sci+Rep 2017 ; 7 (ä): ä Nephropedia Template TP
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TCRP1 transcriptionally regulated by c-Myc confers cancer chemoresistance in tongue and lung cancer #MMPMID28623290
Jia X; Zhang Z; Luo K; Zheng G; Lu M; Song Y; Liu H; Qiu H; He Z
Sci Rep 2017[]; 7 (ä): ä PMID28623290show ga
Previously, we cloned a new gene termed ?tongue cancer resistance-associated protein 1? (TCRP1), which modulates tumorigenesis, enhances cisplatin (cDDP) resistance in cancers, and may be a potential target for reversing drug resistance. However, the mechanisms for regulating TCRP1 expression remain unclear. Herein, we combined bioinformatics analysis with luciferase reporter assay and ChIP assay to determine that c-Myc could directly bind to TCRP1 promoter to upregulate its expression. TCRP1 upregulation in multidrug resistant tongue cancer cells (Tca8113/PYM) and cisplatin-resistant A549 lung cancer cells (A549/DDP) was accompanied by c-Myc upregulation, compared to respective parental cells. In tongue and lung cancer cells, siRNA-mediated knockdown of c-Myc led to decrease TCRP1 expression, whereas overexpression c-Myc did the opposite. Moreover, TCRP1 knockdown attenuated chemoresistance resulting from c-Myc overexpression, but TCRP1 overexpression impaired the effect of c-Myc knockdown on chemosensitivity. Additionally, in both human tongue and lung cancer tissues, c-Myc protein expression positively correlated with TCRP1 protein expression and these protein levels were associated with worse prognosis for patients. Combined, these findings suggest that c-Myc could transcriptionally regulate TCRP1 in cell lines and clinical samples and identified the c-Myc-TCRP1 axis as a negative biomarker of prognosis in tongue and lung cancers.