ELL2 Is Downregulated and Associated with Galactose-Deficient IgA1 in IgA Nephropathy. Disease markers BACKGROUND:Galactose-deficient IgA1 (Gd-IgA1) is an important causal factor in IgA nephropathy; however, the underlying mechanism for the production of Gd-IgA1 is unknown. The elongation factor for RNA polymerase II (ELL2), which encoded a key component of the superelongation complex (SEC), drives secretory-specific Ig mRNA production. METHODS:We enrolled 21 patients with IgAN, 18 healthy controls, and 20 patients with non-IgAN glomerulonephritis. The differential expression of ELL2 was compared using publically available data from Gene Expression Omnibus (GEO) datasets. The relationship between ELL2 expressions and galactose-deficient IgA1 (Gd-IgA1) levels in serum were also studied. At last, the results were validated by shELL2 treatment experiment. RESULTS:We found that the number of CD19+ B cells was increased in IgAN patients compared to healthy controls. The expression level of ELL2 in patients with IgAN was significantly lower than that of healthy control and disease control. Consistent with present results, the lower ELL2 expression in IgAN patients was observed in microarray expression profiles from GEO datasets. Pearson correlation analysis showed that ELL2 expression negatively correlated with Gd-IgA1 levels. Furthermore, in an in vitro experiment, we found that loss of ELL2 function in human B lymphoma DAKIKI cells, an IgA1-producing cell line, increased the levels of Gd-IgA1, which confirmed that ELL2 modulated the levels of Gd-IgA1. CONCLUSION:Our findings implied that decreased ELL2 expression was negatively correlated with the numbers of B cells and aberrant glycosylation of IgA1 in IgAN. 10.1155/2019/2407067

ELL2 Is Required for the Growth and Survival of AR-Negative Prostate Cancer Cells. Cancer management and research BACKGROUND:Elongation factor for RNA polymerase II 2 (ELL2) was reported as a putative tumor suppressor in the prostate. ELL2 is frequently down-regulated in prostatic adenocarcinoma specimens, and loss of ELL2 induced murine prostatic intraepithelial neoplasia and enhanced AR-positive prostate cancer cell proliferation. However, the ELL2 gene appears to be amplified in AR-negative neuroendocrine prostate tumors, suggesting a potential oncogenic role for ELL2 in AR-negative prostate cancer cells. In this study, we explored the potential function of ELL2 in PC-3 and DU145, two AR-negative prostate cancer cell lines. MATERIALS AND METHODS:The role of ELL2 in PC-3 and DU145 cells was studied using siRNA-mediated ELL2 knockdown. Genes regulated by ELL2 knockdown in PC-3 cells were identified and analyzed using RNA-Seq and bioinformatics. The expression of representative genes was confirmed by Western blot and/or quantitative PCR. Cell growth was determined by BrdU, MTT and colony formation assays. Cell death was analyzed by 7-AAD/Annexin V staining and trypan blue exclusion staining. Cell cycle was determined by PI staining and flow cytometry. RESULTS:ELL2 knockdown inhibited the proliferation of PC-3 and DU145 cells. RNA-Seq analysis showed an enrichment in genes associated with cell death and survival following ELL2 knockdown. The interferon-γ pathway was identified as the top canonical pathway comprising of 55.6% of the genes regulated by ELL2. ELL2 knockdown induced an increase in STAT1 and IRF1 mRNA and an induction of total STAT1 and phosphorylated STAT1 protein. Inhibition of cell proliferation by ELL2 knockdown was partly abrogated by STAT1 knockdown. ELL2 knockdown inhibited colony formation and induced apoptosis in both PC-3 and DU145 cells. Furthermore, knockdown of ELL2 caused S-phase cell cycle arrest, inhibition of CDK2 phosphorylation and cyclin D1 expression, and increased expression of cyclin E. CONCLUSION:ELL2 knockdown in PC-3 and DU145 cells induced S-phase cell cycle arrest and profound apoptosis, which was accompanied by the induction of genes associated with cell death and survival pathways. These observations suggest that ELL2 is a potential oncogenic protein required for survival and proliferation in AR-negative prostate cancer cells. 10.2147/CMAR.S248854

Anti-apoptotic factor Birc3 is up-regulated by ELL2 knockdown and stimulates proliferation in LNCaP cells. Wang Zhi,Zhong Mingming,Song Qiong,Pascal Laura E,Yang Zhenyu,Wu Zeyu,Wang Ke,Wang Zhou American journal of clinical and experimental urology ELL2 is a potential tumor suppressor in prostate cancer. ELL2 knockout in mice induced mPIN, the putative precursor of prostate cancer and ELL2 knockdown enhanced proliferation in cultured prostate cancer cells. To explore the mechanism of ELL2 action in prostate cancer, we investigated the role of Birc3, an apoptosis inhibitor, in prostate cancer cells and the regulation of its expression by ELL2. ELL2 knockdown enhanced Birc3 expression in LNCaP and C4-2 cell line models. BrdU assay showed that Birc3 knockdown inhibited proliferation, ELL2 knockdown enhanced proliferation, and Birc3 knockdown counteracted ELL2 knockdown-induced proliferation in LNCaP cells. Trypan blue assay suggested that Birc3 knockout did not induce cell death in LNCaP cells. These findings suggested that Birc3 is a downstream gene of ELL2 and may play a role in driving prostate cancer proliferation.