MicroRNA 506 regulates expression of PPAR alpha in hydroxycamptothecin-resistant human colon cancer cells.
Chemotherapeutic drug resistance remains a major obstacle to the successful treatment of colon cancer. Here, we show that 77 differentially expressed miRNAs were identified in SW1116/HCPT versus SW1116, and over-expressed miR-506 in SW1116/HCPT cells was validated. Then it was indicated that PPARα is a common target of miR-506 by using a luciferase reporter assay. Our results also demonstrated that cytotoxic ability of HCPT requires the concomitant presence of PPARα, and that loss of PPARα expression imparts resistance to HCPTs anti-tumor effects. All together, our studies indicate that miR-506 over-expression in established HCPT-resistant colon cancer cell line confers resistance to HCPT by inhibiting PPARα expression, then providing a rationale for the development of miRNA-based strategies for reversing resistance in HCPT-resistant colon cancer cells.
Division of Gastroenterology and Hepatology, Shanghai Jiao-Tong University School of Medicine, Renji Hospital, Shanghai, China.
Jin Lu
JL
Tong
Chen Peng
CP
Zhang
Fang
F
Nie
Xi Tao
XT
Xu
Ming Ming
MM
Zhu
Shu Dong
SD
Xiao
Zhi Hua
ZH
Ran
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; C561508:MIRN506 microRNA, human; D035683:MicroRNAs; D047493:PPAR alpha; C120029:homocamptothecin; D002166:Camptothecin