title: miR-375 is down-regulated in squamous cervical cancer and inhibits cell migration and invasion via targeting transcription factor SP1.
abstract: Pelvic lymph node metastases are regarded as the most important risk factor and a predictor of poor prognosis for patients with cervical cancer. Exploration of metastasis-related molecules is helpful toward improving the prognosis in cervical cancer. To identify the role of miR-375 in metastasis and progression of cervical cancer, we examined the expression of miR-375 in 170 cervical cancer tissues and 68 normal cervical tissues, using stem-loop quantitative PCR, and found that the expression of miR-375 in cervical cancer tissues was significantly decreased by 4.45-fold, compared with 68 normal tissues. A significant correlation existed between miR-375 expression and clinicopathologic parameters, including lymph node metastasis of cervical cancer. Overexpressed miR-375 suppressed cell proliferation, blocked G1-to-S cell-cycle transition, and inhibited cell migration and invasion in human cervical SiHa and CaSki cells. SP1, a potential target gene of miR-375, was inversely correlated with miR-375 expression in cervical cancer tissues. Moreover, SP1 was negatively regulated by miR-375, and knockdown of SP1 by siRNA inhibited cell malignant behaviors. Thus, our findings suggest that down-regulated miR-375 promotes cell malignant behaviors via the target gene SP1 and may consequently contribute to the progression of cervical cancer.
authors.affiliation: Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Fenfen
authors.initials: F
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Jiansong
authors.initials: J
authors.lastname: Zhou
authors.forename: Junfen
authors.initials: J
authors.lastname: Xu
authors.forename: Chanjuan
authors.initials: C
authors.lastname: Peng
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.forename: Yuanming
authors.initials: Y
authors.lastname: Shen
authors.forename: Weiguo
authors.initials: W
authors.lastname: Lu
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wan
authors.forename: Xing
authors.initials: X
authors.lastname: Xie
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000502:physiology; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008207:Lymphatic Metastasis; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D012334:RNA, Neoplasm / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm; D016329:Sp1 Transcription Factor