title: Regulator of G-protein signaling 4: A novel tumor suppressor with prognostic significance in non-small cell lung cancer.
abstract: Regulator of G-protein signaling (RGS) family members are regulatory molecules which act as GTPase activating proteins (GAPs) for G alpha subunits of heterotrimeric G proteins. Emerging data indicated that RGS members were involved with tumorigenesis and metastasis. In the current study, we identified RGS4 as a novel tumor suppressor with prognostic significance in non-small cell lung cancer (NSCLC). To be specific, we found that RGS4 expression was higher in normal lung tissues than NSCLC specimens (P = 0.003). Further studies demonstrated that RGS4 was generally down-regulated in NSCLC specimens compared with the matched normal lung tissues, both at mRNA and protein levels. In addition, correlational analysis indicated that RGS4 expression levels negatively correlated with lymph node metastasis (P = 0.009) and TNM stage (P = 0.008). Survival analysis demonstrated that patients with lower RGS4 protein expression exhibited a much worse 5-year overall survival and 5-year disease-free survival than those with high expression. More importantly, we proved that over-expression of RGS4 in NSCLC cells decreased invasion and migration due to inhibition of MMP2/9 and reversal of EMT while down-regulation of RGS4 in normal lung cell lines promoted invasion and migration. At last, nude mice metastatic model proved that over-expression of RGS4 suppressed tumor metastasis in vivo. All of these results confirmed the critical role of RGS4 in NSCLC progression.
authors.affiliation: Department of Thoracic Surgery, Qilu Hospital, Shandong University, 107 Wenhua Xi Road, Jinan, China.
authors.forename: Chuanle
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Thoracic Surgery, Qilu Hospital, Shandong University, 107 Wenhua Xi Road, Jinan, China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Yue
authors.affiliation: Department of Thoracic Surgery, Qilu Hospital, Shandong University, 107 Wenhua Xi Road, Jinan, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Qilu Hospital, Shandong University, 107 Wenhua Xi Road, Jinan, China.
authors.forename: Shuhai
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Qilu Hospital, Shandong University, 107 Wenhua Xi Road, Jinan, China.
authors.forename: Cun
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Thoracic Surgery, Qilu Hospital, Shandong University, 107 Wenhua Xi Road, Jinan, China.
authors.forename: Libo
authors.initials: L
authors.lastname: Si
authors.affiliation: Department of Thoracic Surgery, Qilu Hospital, Shandong University, 107 Wenhua Xi Road, Jinan, China. Electronic address: tianhuiql@sohu.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Tian
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality* / Q000556:secondary; D002681:China / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020710:RGS Proteins / Q000378:metabolism*; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D020710:RGS Proteins; D025521:Tumor Suppressor Proteins; C098799:RGS4 protein
keywords: Invasion and migration; NSCLC; Prognosis; RGS4; Survival