title: Nuclear Drosha enhances cell invasion via an EGFR-ERK1/2-MMP7 signaling pathway induced by dysregulated miRNA-622/197 and their targets LAMC2 and CD82 in gastric cancer.
abstract: Drosha is an RNA III-like enzyme that has an aberrant expression in some tumors. Our previous studies showed the aberrant Drosha in gastric tumors. However, the roles of nuclear Drosha, the main regulator of microRNA (miRNA) biogenesis, in gastric cancer (GC) progression remain poorly understood. In this study, we demonstrated that nuclear Drosha is significantly associated with cell invasion of GC and that Drosha silence impedes the tumor invasion. Knockdown of Drosha led to a set of dysregulated miRNAs in GC cells. Multiple targets of these miRNAs were the members in cell migration, invasion and metastasis-associated signaling (e.g. ECM-receptor interaction, focal adhesion, p53 signaling and MAPK signaling pathway) revealed by bioinformatics analysis. LAMC2 (a key element of ECM-receptor signaling) and CD82 (a suppressor of p53 signaling) are the targets of miR-622 and miR-197, respectively. High levels of LAMC2 and low levels of CD82 were significantly related to the worse outcome for GC patients. Furthermore, overexpression of LAMC2 and knockdown of CD82 markedly promoted GC cell invasion and activated EGFR/ERK1/2-MMP7 signaling via upregulation of the expression of phosphorylated (p)-EGFR, p-ERK1/2 and MMP7. Our findings suggest that nuclear Drosha potentially has a role in the development of GC.
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Liyun
authors.initials: L
authors.lastname: Xu
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.|Experimental Teaching Center of Basic Medicine Science, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Tu
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yan-E
authors.initials: YE
authors.lastname: Du
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Siyang
authors.initials: S
authors.lastname: Wen
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Tang
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Yin
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lang
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Kexin
authors.initials: K
authors.lastname: Sun
authors.affiliation: Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Guanglun
authors.initials: G
authors.lastname: Yang
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Tang
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Manran
authors.initials: M
authors.lastname: Liu
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D066246:ErbB Receptors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D051861:Kangai-1 Protein / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology; D010766:Phosphorylation / Q000502:physiology; D043244:Ribonuclease III / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology
chemical_list: C497688:CD82 protein, human; D051861:Kangai-1 Protein; C400567:LAMC2 protein, human; D007797:Laminin; D035683:MicroRNAs; C512478:EGFR protein, human; D066246:ErbB Receptors; C517918:DROSHA protein, human; D043244:Ribonuclease III; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7