miR-107 activates ATR/Chk1 pathway and suppress cervical cancer invasion by targeting MCL1.
MicroRNAs (miRNAs) are a class of single-stranded, non-coding RNAs of about 22 nucleotides in length. Increasing evidence implicates miRNAs may function as oncogenes or tumor suppressors. Here we showed that miR-107 directly targeted MCL1 and activated ATR/Chk1 pathway to inhibit proliferation, migration and invasiveness of cervical cancer cells. Moreover, we found that MCL1 was frequently up-regulated in cervical cancer, and knockdown of MCL1 markedly inhibited cancer cell proliferation, migration and invasion, whereas ectopic expression of MCL1 significantly enhances these properties. The restoration of MCL1 expression can counteract the effect of miR-107 on the cancer cells. Together, miR-107 is a new regulator of MCL1, and both miR-107 and MCL1 play important roles in the pathogenesis of cervical cancer. We have therefore identified a mechanism for ATR/Chk1 pathway which involves an increase in miR-107 leading to a decrease in MCL1. Correspondingly, our results revealed that miR-107 affected ATR/Chk1 signalling and gene expression, and implicated miR-107 as a therapeutic target in human cervical cancer. We also demonstrated that taxol attenuated migration and invasion in cervical cancer cells by activating the miR-107, in which miR-107 play an important role in regulating the expression of MCL1. Elucidation of this discovered MCL1 was directly regulated by miR-107 will greatly enhance our understanding of the mechanisms responsible for cervical cancer and will provide an additional arm for the development of anticancer therapies.
Development and Utilization Key Laboratory of Northeast Plant Materials, Key Laboratory of Northeast Authentic Materials Research and Development in Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenhe District, Shenyang, 110016, China.
Chengyan
C
Zhou
Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Baojian Road 157, Nangang District, Harbin, 150081, China.
Gang
G
Li
Development and Utilization Key Laboratory of Northeast Plant Materials, Key Laboratory of Northeast Authentic Materials Research and Development in Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenhe District, Shenyang, 110016, China.
Jingjing
J
Zhou
Development and Utilization Key Laboratory of Northeast Plant Materials, Key Laboratory of Northeast Authentic Materials Research and Development in Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenhe District, Shenyang, 110016, China.
Na
N
Han
Development and Utilization Key Laboratory of Northeast Plant Materials, Key Laboratory of Northeast Authentic Materials Research and Development in Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenhe District, Shenyang, 110016, China.
Zhihui
Z
Liu
Development and Utilization Key Laboratory of Northeast Plant Materials, Key Laboratory of Northeast Authentic Materials Research and Development in Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenhe District, Shenyang, 110016, China.
Jun
J
Yin
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D000071877:Checkpoint Kinase 1; D015536:Down-Regulation; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D000972:Antineoplastic Agents, Phytogenic; C579095:MCL1 protein, human; C549045:MIRN107 microRNA, human; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D011494:Protein Kinases; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; D017239:Paclitaxel