title: MYCN-mediated miR-21 overexpression enhances chemo-resistance via targeting CADM1 in tongue cancer.
abstract: Chemo-resistance is still a major obstacle in successful cancer treatment. Previously, we found that miR-21 (miR-21-5p) was upregulated in drug-resistant tongue cancer (TC) cell line Tca8113/PYM. However, the mechanisms for miR-21 upregulation and its role in chemo-resistance in TC remain unclear. Here, we demonstrated that functional inhibition of miR-21 sensitized TC cells to chemotherapy. In agreement, overexpressed miR-21 enhanced chemo-resistance in TC cells. We found that miR-21 directly targeted CADM1 expression, which was downregulated in drug-resistant TC cells. Restored CADM1 expression sensitized TC cells to chemotherapy, but CADM1 knockdown induced chemo-resistance. Mechanically, CADM1 interacted with BMI1 to inhibit its nuclear translocation. Moreover, MYCN which was overexpressed in drug-resistant TC cells directly bound to the miR-21 promoter to upregulated miR-21 expression in TC cells. Importantly, the expression levels of miR-21 and CADM1 negatively correlated, but MYCN and miR-21 positively correlated in TC tissues. High levels of miR-21 and MYCN and low level of CADM1 were associated with poor prognosis in TC patients. In conclusion, our study suggests an important role of the MYCN/miR-21/CADM1 axis in chemo-resistance in TC patients and may lead to promising prognostic biomarkers and novel treatment strategies to improve the chemotherapeutic efficacy for TC patients.
  
  
  
  MiR-21 enhances chemo-resistance via targeting CADM1 in tongue cancer cells. CADM1 sensitizes tongue cancer cells to chemotherapy. CADM1 interacts with BMI1 to inhibit its nuclear translocation. MYCN transcriptionally regulates miR-21 expression. Dysregulated MYCN/miR-21/CADM1 axis associates with poor prognosis in TC patients.
authors.affiliation: Cancer Center of Guangzhou Medical University, Cancer Research Institute of Guangzhou Medical University; Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
authors.forename: Guopei
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Cancer Center of Guangzhou Medical University, Cancer Research Institute of Guangzhou Medical University; Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Cancer Center of Guangzhou Medical University, Cancer Research Institute of Guangzhou Medical University; Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Jia
authors.affiliation: Cancer Center of Guangzhou Medical University, Cancer Research Institute of Guangzhou Medical University; Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Peng
authors.affiliation: Cancer Center of Guangzhou Medical University, Cancer Research Institute of Guangzhou Medical University; Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
authors.forename: Liyun
authors.initials: L
authors.lastname: Luo
authors.affiliation: Cancer Center of Guangzhou Medical University, Cancer Research Institute of Guangzhou Medical University; Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
authors.forename: Yingen
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Cancer Center of Guangzhou Medical University, Cancer Research Institute of Guangzhou Medical University; Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Yin
authors.affiliation: Cancer Center of Guangzhou Medical University, Cancer Research Institute of Guangzhou Medical University; Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.affiliation: Cancer Center of Guangzhou Medical University, Cancer Research Institute of Guangzhou Medical University; Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Cancer Center of Guangzhou Medical University, Cancer Research Institute of Guangzhou Medical University; Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
authors.forename: Minying
authors.initials: M
authors.lastname: Lu
authors.affiliation: Cancer Center of Guangzhou Medical University, Cancer Research Institute of Guangzhou Medical University; Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Cancer Center of Guangzhou Medical University, Cancer Research Institute of Guangzhou Medical University; Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Cancer Center of Guangzhou Medical University, Cancer Research Institute of Guangzhou Medical University; Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China. hezhimin2005@yahoo.com.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: He
mesh_terms: D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D000071447:N-Myc Proto-Oncogene Protein / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D014062:Tongue Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: C403514:CADM1 protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C524940:MIRN21 microRNA, human; C459801:MYCN protein, human; D035683:MicroRNAs; D000071447:N-Myc Proto-Oncogene Protein; D012333:RNA, Messenger
keywords: CADM1; Drug resistance; MYCN; Tongue cancer; miR-21