title: MiR-124 down-regulation is critical for cancer associated fibroblasts-enhanced tumor growth of oral carcinoma.
abstract: Cancer associated fibroblasts (CAFs) are known to be involved in initiation, progression and metastasis of various cancers. However, the molecular mechanism of how CAFs affects the biological function of oral cancer (OC) has not been fully-addressed. In this study, we demonstrated that miR-124 was downregulated in oral CAFs and oral cancer cells (OCCs) when compared with matched normal fibroblasts (NFs). Hypermethylation in the promoter region of miR-124 genes was accounted for its downregulation. Interestingly, CAFs but not NFs exerted promotion effect on OCCs cell proliferation, migration and tumor growth in CAFs/NFs-OCCs co-culture. Furthermore, we identified Chemokine (C-C motif) ligand 2 (CCL2) and Interleukin 8 (IL-8) as two direct targets of miR-124. Over-expression of miR-124 in CAFs-OCCs co-culture abrogated CAFs-promoted OCCs cell growth and migration, and this inhibitory effect can be rescued by addition of CCL2 and IL-8. Finally, we showed that restoration of miR-124 expression by lentiviral infection or formulated miR-124 injection inhibited oral tumor growth in vivo suggesting miR-124 rescue could be a potential rationale for therapeutic applications in oral cancer in the future.
authors.affiliation: Department of Stomatology, School of Stomatology and medicine, Foshan Stomatology Hospital, Foshan University, Foshan 528000, PR China. Electronic address: dentistlx@163.com.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, Cancer Center, Chenzhou No.1 People's Hospital, Chenzhou 423000, PR China.
authors.forename: Qinqiao
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Department of Head and Neck Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Center South University, Changsha 410013, PR China.
authors.forename: Jinyun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Stomatology, School of Stomatology and medicine, Foshan Stomatology Hospital, Foshan University, Foshan 528000, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Stomatology, School of Stomatology and medicine, Foshan Stomatology Hospital, Foshan University, Foshan 528000, PR China.
authors.forename: Yangcong
authors.initials: Y
authors.lastname: Gu
mesh_terms: D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic
chemical_list: D018932:Chemokine CCL2; D016209:Interleukin-8; C509207:MIRN124 microRNA, human; D035683:MicroRNAs
keywords: Cancer associated fibroblasts (CAFs); Chemokine (C-C motif) ligand 2; Interleukin 8; MiR-124; Oral squamous cell carcinoma