Human Rad23A plays a regulatory role in autophagy.
Chemotherapeutic agents can upregulate autophagy which contributes to the acquisition of chemoresistance and the recurrence of cancer. The involvement of hHR23A in chemoresistance is unknown. In this study, we provide evidence suggesting that hHR23A may regulate autophagy. Knockdown of hHR23A decreased cell growth and increased the resistance in A549 cells to the DNA-damaging agents, cisplatin and oxaliplatin. Measurement of EGFP-LC3 puncta (a marker of autophagy) revealed that autophagy was increased in hHR23A-depleted cells. This effect was augmented by exposure to cisplatin or oxaliplatin. In contrast, the overexpression of hHR23A reversed the levels of autophagy-related proteins to control levels in hHR23A-knockdown cells. Moreover, we observed direct interactions among hHR23A, Beclin 1, and LC3. Finally, 3-methyladenine (3-MA)-induced inhibition of autophagy was found to reverse the sensitivity of hHR23A-knockdown cells to the tested DNA-damaging agents. These results collectively indicated that hHR23A-depleted cells exhibit enhanced autophagy when treated with DNA-damaging agents, perhaps suggesting a basis for the involvement of hHR23A in the acquired chemoresistance of cancer cells. Our study thus reveals a previously unrecognized autophagic function for hHR23A and suggests that it could be a potential therapeutic target for chemosensitizing resistant cancer cells.
Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan.
Xiaotong
X
Tan
Bachelor Program of Biotechnology, National Chung Hsing University, Taichung 40227, Taiwan.
Hsin-Chiao
HC
Wang
Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan.
Ruei-Yue
RY
Liang
Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan; Department of Nursing, Asia University, Taichung 41354, Taiwan. Electronic address: smchuang@dragon.nchu.edu.tw.
Show-Mei
SM
Chuang
D000072283:A549 Cells; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D000071186:Beclin-1 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D011485:Protein Binding; D034622:RNA Interference
D000970:Antineoplastic Agents; C491997:BECN1 protein, human; D000071186:Beclin-1; D004268:DNA-Binding Proteins; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C086985:RAD23A protein, human; C025946:3-methyladenine; D045643:DNA Repair Enzymes; D000225:Adenine; D002945:Cisplatin
Autophagy; Chemoresistance; LC3; hHR23A