title: The association of the expression of miR-122-5p and its target ADAM10 with human breast cancer.
abstract: MicroRNAs can regulate many biological functions. miR-122-5p has a tumor suppressor function through different molecular pathways. Also, our second hit, ADAM10, targeted by miR-122-5p, is a major determinant of HER2 shedding causing that trastuzumab cannot bind to HER2 receptors. Therefore, our analysis upon ADAM10 expression and miR-122-5p was a good point to understand molecular mechanism of breast cancer. In our study, we investigated the expression profiles of miR-122-5p and its target ADAM10 in 71 breast cancer patients. Immunohistochemical analysis of ER, PR and HER2 gene products was used to categorize tumors in patients. Expression data and immunohistochemical findings were evaluated to comment on the relationship between miR-122-5p and ADAM10. ADAM10 expression was higher in tumor than that of normal tissue but miR-122-5p expression was lower in tumor than that of normal tissue. The expression pattern in HER2+ patients was reverse of the overall result. It can be explained like that miR-122-5p expression increases especially in HER2+ cancer cell to suppress ADAM10 shedding activity on HER2 receptor. However, increase in expression of tumor suppressor miR-122-5p is not enough to inhibit ADAM10. All in all, we can think miR-122-5p as potential regulator of ADAM10 and trastuzumab resistance. Since if we increase miR-122-5p activity together with trastuzumab administration, then HER2+ breast cancer cells may overcome trastuzumab resistance by inhibiting ADAM10 shedding activity on HER2 receptors and increase the efficiency of trastuzumab.
authors.affiliation: Department of Medical Biology, Faculty of Medicine, University of Gaziantep, Şehitkamil, 27310, Gaziantep, Turkey, sercanergun@msn.com.
authors.forename: Sercan
authors.initials: S
authors.lastname: Ergün
authors.forename: Mustafa
authors.initials: M
authors.lastname: Ulasli
authors.forename: Yusuf Ziya
authors.initials: YZ
authors.lastname: Igci
authors.forename: Mehri
authors.initials: M
authors.lastname: Igci
authors.forename: Sevil
authors.initials: S
authors.lastname: Kırkbes
authors.forename: Ersin
authors.initials: E
authors.lastname: Borazan
authors.forename: Ahmet
authors.initials: A
authors.lastname: Balik
authors.forename: Önder
authors.initials: Ö
authors.lastname: Yumrutaş
authors.forename: Celalettin
authors.initials: C
authors.lastname: Camci
authors.forename: Ecir Ali
authors.initials: EA
authors.lastname: Cakmak
authors.forename: Ahmet
authors.initials: A
authors.lastname: Arslan
authors.forename: Serdar
authors.initials: S
authors.lastname: Oztuzcu
mesh_terms: D020413:3' Untranslated Regions; D051722:ADAM Proteins / Q000235:genetics*; D000072197:ADAM10 Protein; D000328:Adult; D000368:Aged; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics* / Q000601:surgery; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; C531907:MIRN122 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human