Overexpression of RhoE in non-small cell lung cancer (NSCLC) is associated with smoking and correlates with DNA copy number changes

Abstract

RhoE, a small G protein, is constitutively GTP bound within the cell and can regulate actin cytoskeleton reorganization, leading to the appearance of aggregates of actin filaments. Although emerging evidence suggests that RhoE is causally involved in cancer formation and progression, little is known about its significance in solid cancer, including lung cancer. In the present study, the expression of RhoE was analyzed using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR), real-time RT-PCR, immunohistochemistry and western blot in 30 patients with Non-small Cell Lung Cancer (NSCLC). Then the correlation of RhoE overexpression with clinical parameters was evaluated. Furthermore, the possible reasons contributing to the RhoE expression were examined by real-time genomic PCR and mutation analysis on DNA sequence and cDNA sequence. Our results revealed that RhoE expression was dramatically increased in lung cancer tissues compared with adjacent nontumoral lung tissues (p < 0.01). Immunohistochemistry showed a strong cytoplasmic staining in cancer cells compared with positive membrane staining in adjacent nontumoral proliferative alveolar epitheliums. Moreover, the overexpression of RhoE was significantly associated with the patients' smoking history (p < 0.05). 72% tumor tissues displayed DNA copy number changes based on the DNA levels in the matched adjacent nontumoral lung tissues and this copy number changes correlated significantly with RhoE expression and smoking history (p < 0.05). Three polymorphisms were identified but no correlation was found with the clinicopathological features. To our knowledge, this is the first report demonstrating that overexpression of RhoE correlated with smoking and DNA copy number changes, suggesting that RhoE may serve as a molecular marker to identify high-risk individuals and assist in the identification of additional pathways of carcinogenesis.

microRNA-802/Rnd3 pathway imposes on carcinogenesis and metastasis of fine particulate matter exposure

“…In the non-small cell lung cancer tissues, the expression of Rnd3, mRNA, and protein levels were dramatically increased, compared to that of adjacent non-tumoral lung tissues. Moreover, overexpression of Rnd3 was correlated to patients’ smoking history [36]. Together with our study, overexpression of Rnd3 in lung tissue could be induced by environmental stresses.…”

Rnd3 Regulates Lung Cancer Cell Proliferation through Notch Signaling

“…Interestingly, as a gene highly related to tumors, research on the role of Rnd3 in NSCLC is extremely deficient. Two studies showed that Rnd3 over-expression may be associated with an unfavorable prognosis in NSCLC patients [27], [28] while the precise role of Rnd3 in NSCLC has not yet been investigated. Here, we reported that Rnd3 is down-regulated in H358, H520 and A549 cells, and this down-regulation promotes the growth of these two cell lines and is dependent upon up-regulated Notch signaling.…”

Pathophysiological Functions of Rnd 3/ RhoE

“…Our lab recently revealed that RND3 is substantially downregulated in glioblastoma multiform (GBM), and this downregulation is negatively associated with the clinical progression and prognosis of patients (manuscript submitted). However, results from non-small cell lung cancer (30, 148), colorectal carcinoma (153), pancreatic cancer (50), and gastric carcinoma (35) studies showed that high RND3 expression positively correlated with tumor progression. However, there is some controversy over the results from lung cancer and colorectal carcinoma observations.…”