miR-124 and miR-506 inhibit colorectal cancer progression by targeting DNMT3B and DNMT1.
miR-124 and miR-506 are reportedly down-regulated and associated with tumor progression in many cancers, but little is known about their intrinsic regulatory mechanisms in colorectal cancer (CRC). In this study, we found that the miR-124 and miR-506 levels were significantly lower in human CRC tissues than in controls, as indicated by qRT-PCR and in situ hybridization histochemistry. We also found that the overexpression of miR-124 or miR-506 inhibited tumor cell progression and increased sensitivity to chemotherapy in vitro. Increased miR-124 or miR-506 expression also inhibited tumor cell proliferation and invasion in vivo. Luciferase reporter assays and western blotting were used to determine the association between miR-124, miR-506 and their target genes, DNMTs. We further identified that miR-124 and miR-506 directly targeted DNMT3B and indirectly targeted DNMT1. The overexpression of miR-124 and miR-506 reduced global DNA methylation and restored the expression of E-cadherin, MGMT and P16. In conclusion, our data showed that miR-124 and miR-506 inhibit progression and increase sensitivity to chemotherapy by targeting DNMT3B and DNMT1 in CRC. These findings may provide novel avenues for the development of targeted therapies.
Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Zhiheng
Z
Chen
Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Shaojun
S
Liu
Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Li
L
Tian
Department of Gastroenterology, The Hunan Provincial People's Hospital, Changsha, Hunan, China.
Minghao
M
Wu
Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan, China.
Feiyan
F
Ai
Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Wuliang
W
Tang
Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan, China.
Lian
L
Zhao
Department of Oncology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Juan
J
Ding
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Liyang
L
Zhang
Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan, China.
Anliu
A
Tang
D000818:Animals; D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000494:pharmacology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D045325:HCT116 Cells; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000097584:DNA Methyltransferase 3B
D015703:Antigens, CD; D000970:Antineoplastic Agents; D015820:Cadherins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D015254:DNA Modification Methylases; D045643:DNA Repair Enzymes; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; D000097584:DNA Methyltransferase 3B; C513384:CDH1 protein, human; C509207:MIRN124 microRNA, human; C561508:MIRN506 microRNA, human; C000619380:DNMT1 protein, human; C000619381:Dnmt1 protein, mouse; C515491:MGMT protein, human
DNMT1; DNMT3B; colorectal cancer; miR-124; miR-506