miR-20a targets BNIP2 and contributes chemotherapeutic resistance in colorectal adenocarcinoma SW480 and SW620 cell lines.
Chemotherapy is an important treatment for colorectal adenocarcinoma cancer; however, colorectal adenocarcinoma cells often develop resistance to chemotherapeutic drugs, leading to relapse and poor patient prognosis. The development of drug resistance is often a multifactor process, which involved several genes and cellular mechanisms. microRNAs are endogenous small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. In the present study, we investigated the possible role of microRNAs in regulating drug sensitivity of colorectal adenocarcinoma cells SW620 and SW480. Using microRNA expression arrays and quantitative reverse transcriptase (RT)-PCR, we found that SW620 cells exhibited elevated miR-20a expression compared with SW480 cells. In addition, these two cell lines displayed different sensitivities to the chemotherapeutic drugs fluorouracil, oxaliplatin, and teniposide. Modulation of miR-20a altered the sensitivity of SW620 and SW480 cells to these drugs; knockdown of miR-20a sensitized SW620 cells to chemotherapeutic agents, whereas overexpression of miR-20a in SW480 cells resulted in chemoresistance. Endogenous BNIP2 mRNA and BNIP2 protein levels were inversely related to miR-20a levels as detected by quantitative RT-PCR and western blot analysis. Fluorescence reporter assays showed a direct interaction between miR-20a and the BNIP2 3'UTR. Taken together, our findings suggested that miR-20a may play a role in colorectal adenocarcinoma cancer cell drug resistance and may be a therapeutic target against chemotherapy drug resistance in colorectal adenocarcinoma.
Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, Tianjin, China.
Huijuan
H
Chai
Min
M
Liu
Ruiqing
R
Tian
Xin
X
Li
Hua
H
Tang
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D005472:Fluorouracil / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin; D013713:Teniposide / Q000627:therapeutic use
D000970:Antineoplastic Agents; C499184:BNIP2 protein, human; D002352:Carrier Proteins; C534451:MIRN20a microRNA, human; D035683:MicroRNAs; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D013713:Teniposide; D005472:Fluorouracil