Lentiviral Vector Mediated Delivery of RHBDD1 shRNA down Regulated the Proliferation of Human Glioblastoma Cells

Abstract

Abbreviation: RHBDD1: Rhomboid Domain Containing 1; shRNA: Short Hairpin RNAs; RNAi: RNA Interference.Rhomboid domain containing 1 (RHBDD1) gene, a new member of rhomboid family of proteins is highly responsible for the regulation of apoptosis by cleaving pro-apoptotic Bcl-2 family protein BIK. Therefore, the higher expression levels of RHBDD1 in cancer tissues may have a direct influence on cancer progression by arresting apoptosis. With this background this study was focused to find out the effect of RHBDD1 silencing on the progression of human brain glioblastoma cells, U251 and U87MG. The results indicated that both cell lines show a higher expression level of RHBDD1 and RNA interference (RNA) mediated gene silencing successfully down regulated the RHBDD1 gene expression. As a result of RHBDD1 silencing the proliferation of both cell types was reduced by over 50%, 5 days after silencing. Moreover the colony formation was completely inhibited and there were no cells present following two week RHBDD1 gene silencing. The cell proliferation was inhibited as a result of cell cycle arrest due to RHBDD1 absence. Therefore, these results clearly indicate that, RHBDD1 is essential for the progression of glioblastoma cells and silencing of it is resulting in significant inhibition of cell cycle progression and cell proliferation. Collectively, this study shows that RHBDD1 gene engineering could be used as an effective tool in malignant brain tumor therapy.

MiR-924 as a tumor suppressor inhibits non-small cell lung cancer by inhibiting RHBDD1/Wnt/β-catenin signaling pathway

“…Using public microarray datasets, higher RHBDD1 expression in NSCLC patients had much shorter overall survival rates. Although RHBDD1 as a target gene by miRNAs was rarely reported in diseases, RHBDD1 has been frequently confirmed to be highly expressed in human cancers, such as colorectal cancer, glioblastoma, hepatocellular carcinoma, and chronic myeloid leukemia, whose knockdown inhibits the proliferation of these tumor cells [ 15 , 16 , 30 , 31 ]. Our data further demonstrated that RHBDD1 knockdown imitated, while overexpression reversed the effects of miR-924 on NSCLC cell proliferation, migration and invasion, as well as Wnt/β-catenin signaling pathway.…”

“…Rhomboid domain-containing protein 1 (RHBDD1), a new member of the Rhomboid family is highly responsible for the regulation of apoptosis cleaving pro-apoptotic Bcl-2 family protein BIK [14]. Related studies showed that RNA interference (RNA) mediated RHBDD1 silencing significantly suppressed cell proliferation and cell cycle progression in hepatocellular carcinoma [15], glioblastoma [16] and colorectal cancer [17]. Moreover, Zhang et al [18] demonstrated that RHBDD1 could promote tumor metastasis by promoting Wnt/β-catenin signaling and epithelial-mesenchymal transition in colorectal cancer.…”

Silibinin suppresses epithelial–mesenchymal transition in human non-small cell lung cancer cells by restraining RHBDD1

“…Emerging evidence indicates that silencing RHBDD1 suppresses cell growth and proliferation in hepatocellular carcinoma [13], glioblastoma [14] and colorectal cancer [15]. In breast cancer [16,17] and colorectal cancer cells [18], RHBDD1 has been shown to promote migration, invasion and EMT.…”

Rare copy number variants in individuals at clinical high risk for psychosis: Enrichment of synaptic/brain‐related functional pathways

“…RHBDD1 RNA and proteins are expressed in the human brain (Lonsdale et al, ; Uhlén et al, ). Moreover, this gene is implicated in many cancers including brain cancer (Miao et al, ; Wei, Lv, Chen, & Guan, ; Zhang, Zhao, et al, ; Zhang, Miao, et al, ). Nevertheless, currently, there are no studies reporting the role of RHBDD1 in neurodevelopmental disorders.…”