title: miR-3940-5p Functions as a Tumor Suppressor in Non-Small Cell Lung Cancer Cells by Targeting Cyclin D1 and Ubiquitin Specific Peptidase-28.
abstract: miR-3940-5p level was lower in non-small cell lung cancer (NSCLC) tumor tissues than that in the matched tumor-adjacent tissues and correlated with clinicopathological features. Cyclin D1 (CCND1), a key driver of malignant transformation in NSCLC, was overexpressed in many cancers, including NSCLC. The ubiquitin specific peptidase-28 (USP28) was also overexpressed in NSCLC and associated with poor prognosis of NSCLC patients. We searched for miR-3940-5p targets by using TargetScan and miRanda online tools and found that CCND1 and USP28 were potential targets of miR-3940-5p. Based on these findings, we speculated that miR-3940-5p might target CCND1 and USP28 to inhibit NSCLC growth. We determined the expression of miR-3940-5p, CCND1, and USP28 by quantitative real-time polymerase chain reaction and Western blot assays, respectively, and found downregulation of miR-3940-5p and upregulation of CCND1 and USP28 in NSCLC tissues and cell lines. Cell proliferation and apoptosis assays showed that miR-3940-5p suppressed proliferation and promoted apoptosis in NSCLC cells, and silencing CCND1 and USP28 both recapitulated the effects of miR-3940-5p on NSCLC cells. Furthermore, we verified that CCND1 and USP28 were direct targets of miR-3940-5p and also found that the effects of NSCLC cell proliferation and apoptosis by miR-3940-5p were attenuated by overexpression of CCND1 or USP28. The animal experiments also showed that overexpression of miR-3940-5p inhibited the growth of NSCLC tumors in vivo. These results confirmed our speculation that miR-3940-5p inhibits proliferation and induces apoptosis in NSCLC cells by targeting CCND1 and USP28. These findings facilitate a better understanding of the molecular mechanisms underlying NSCLC initiation and progression and provide promising diagnostic markers and therapeutic targets for NSCLC.
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China; Interventional Institute of Zhengzhou University, Zhengzhou 450052, PR China; Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou 450052, PR China.
authors.forename: Kewei
authors.initials: K
authors.lastname: Ren
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China; Interventional Institute of Zhengzhou University, Zhengzhou 450052, PR China; Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou 450052, PR China.
authors.forename: Yahua
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China; Interventional Institute of Zhengzhou University, Zhengzhou 450052, PR China; Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou 450052, PR China.
authors.forename: Huibin
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China; Interventional Institute of Zhengzhou University, Zhengzhou 450052, PR China; Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou 450052, PR China.
authors.forename: Zongming
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China; Interventional Institute of Zhengzhou University, Zhengzhou 450052, PR China; Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou 450052, PR China. Electronic address: hanxinwei2006@163.com.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Han