title: Orai1, a Direct Target of microRNA-519, Promotes Progression of Colorectal Cancer via Akt/GSK3β Signaling Pathway.
abstract: Orai1, which is involved in store-operated calcium entry, has recently been implicated in cancer progression. However, the role of Orai1 in colorectal cancer (CRC) progression remains unclear.
  
  
  
  We used real-time PCR and western blot to measure Orai1 expression in four CRC cell lines, 60 tumor pairs, and corresponding non-tumor tissues from CRC patients. Immunohistochemistry was performed to examine Orai1 expression in CRC and corresponding non-tumor tissues. Statistical analyses were applied to evaluate the prognostic value and associations of Orai1 expression with clinical parameters. Furthermore, the Orai1 gene was overexpressed in HCT116 cell and silenced with siRNA in LOVO cell. Moreover, cell proliferation and apoptosis were measured using MTT assay and flow cytometry, and a molecular mechanism of Orai1 regulation by miR-519 was explored.
  
  
  
  Orai1 expression was higher in CRC tissues than adjacent non-cancerous tissues, and this was positively correlated in CRC patients with distant metastasis and poor prognosis. Also, increased expression of Orai1 was observed in highly invasive CRC cell lines and ectopic expression of Orai1 enhanced cell proliferation and inhibited apoptosis; silencing Orai1 suppressed cell proliferation and induced apoptosis. The Akt/GSK3β pathway contributed to Orai1 effects in CRC cells, and Orai1 was a direct target of miR-519, a microRNA not previously reported to be involved in both CRC tissues and cell lines.
  
  
  
  We identified a novel CRC regulatory circuit involving the miR-519-Orai1 axis, and dysfunction of this drives diverse aspects of CRC pathogenesis.
authors.affiliation: Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng District, Beijing, 100050, China.|National Clinical Research Center of Digestive Diseases, Beijing, 100050, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng District, Beijing, 100050, China.|National Clinical Research Center of Digestive Diseases, Beijing, 100050, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng District, Beijing, 100050, China.|National Clinical Research Center of Digestive Diseases, Beijing, 100050, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng District, Beijing, 100050, China.|National Clinical Research Center of Digestive Diseases, Beijing, 100050, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng District, Beijing, 100050, China.|National Clinical Research Center of Digestive Diseases, Beijing, 100050, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Bai
authors.affiliation: Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng District, Beijing, 100050, China. zhangzhongtao5516@126.com.|National Clinical Research Center of Digestive Diseases, Beijing, 100050, China. zhangzhongtao5516@126.com.
authors.forename: Zhongtao
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D000071740:ORAI1 Protein / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C546194:MIRN519 microRNA, human; D035683:MicroRNAs; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt/GSK3β pathway; Apoptosis; Colorectal cancer; Orai1; miR-519