title: STIM1, a direct target of microRNA-185, promotes tumor metastasis and is associated with poor prognosis in colorectal cancer.
abstract: STIM1 (stromal interaction molecule 1), an endoplasmic reticulum Ca(2+) sensor that triggers the store-operated Ca(2+) entry activation, has recently been implicated in cancer progression. However, the role of STIM1 in the progression and metastasis of colorectal cancer (CRC) has not been addressed. In this study, we confirmed increased expression of STIM1 in highly invasive CRC cell lines. Enhanced expression of STIM1 promoted CRC cell metastasis in vitro and in vivo, whereas silencing of STIM1 with small interfering RNA resulted in reduced metastasis. Ectopic expression of STIM1 in CRC cells induced epithelial-to-mesenchymal transition (EMT), whereas silencing of STIM1 had the opposite effect. Furthermore, STIM1 expression was markedly higher in CRC tissues than in adjacent noncancerous tissues. STIM1 overexpression correlated with poor differentiation and higher tumor node metastasis stage. CRC patients with positive STIM1 expression had poorer prognoses than those with negative STIM1 expression. Moreover, STIM1 was found to be a direct target of miR-185, a microRNA (miRNA) that has not previously been reported to be involved in EMT, in both CRC tissues and cell lines. Taken together, these findings demonstrate for the first time that STIM1 promotes metastasis and is associated with cancer progression and poor prognosis in patients with CRC. In addition, we show that expression of STIM1 is regulated by a posttranscriptional regulatory mechanism mediated by a new EMT-related miRNA. This novel miR-185-STIM1 axis promotes CRC metastasis and may be a candidate biomarker for prognosis and a target for new therapies.
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: B
authors.initials: B
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: N
authors.initials: N
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Q
authors.initials: Q
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Han
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: K
authors.initials: K
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: D
authors.initials: D
authors.lastname: Fan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D011379:Prognosis; D000071737:Stromal Interaction Molecule 1
chemical_list: C552431:MIRN185 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D009363:Neoplasm Proteins; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1