Downregulation of miR-16 via URGCP pathway contributes to glioma growth

Abstract

Experimental and clinical evidence points to a critical role of Upregulator of cell proliferation (URGCP/URG4) in controlling the progression of multiple tumors. However, the oncogenic role of URGCP in glioma still remains elusive. In this study we tried to investigate the oncogenic roles and molecular mechanisms of URGCP in glioma. We found that the levels of URGCP were upregulated in glioma, and that the high-levels of URGCP indicated a worse prognosis in glioma patients. URGCP and miR-16 are critical for glioma growth: silencing URGCP (shURGCP) inhibited glioma growth, while, the shURGCP-mediated proliferative inhibition could be recovered by antagonizing miR-16 (anta-miR-16) in vivo and in vitro. Mechanically, URGCP repressed miR-16 expression via activating NF-κB/c-myc pathway in glioma; Cyclins D1 and Cyclin E1 were identified as the direct targets of miR-16, thus, URGCP-mediated miR-16 downregulation accelerated cell proliferation by upregulating Cyclin D1 and Cyclin E1 expression. All these results suggested that URGCP accelerates glioma growth through the NF-κB/c-myc/miR-16/Cyclin D1/E1 pathway, and both URGCP and miR-16 function as a novel cell cycle regulators in glioma and could be considered as potential targets for glioma therapy.

URG4 mediates cell proliferation and cell cycle in osteosarcoma via GSK3β/β-catenin/cyclin D1 signaling pathway

“…A large number of studies have investigated the potential pathways by which UGR4 regulates tumor cell proliferation and cell cycle progression. Several studies have revealed that UGR4 could control the proliferation and cell cycle progression of tumor cells by regulating cyclin D1 [10,23]. An increase in cell transcription is usually accompanied by an increase in protein translation and a decrease in hydrolysis; thereby, the stability of cyclin D1 is a key factor affecting cell proliferation [39].…”

“…URG4, a novel oncogene located on the short arm of chromosome 7p13, promotes cell proliferation via the MAPK, PI3K, Akt, and NF-kappa B pathways. Studies have shown that high levels of URG4 protein have been found in many solid tumors and are involved in tumorigenesis and tumor development, including hepatocellular carcinoma [6], gastric cancer [7], ovarian cancer [8], glioblastoma [9], glioma [10], breast carcinoma [11], nonsmall-cell lung cancer [12], and nasopharyngeal cancer [13]. Huang et al suggested that URG4 expression in osteosarcoma tissue is closely associated with recurrence, metastasis, and poor prognosis of osteosarcoma [14].…”

Retracted Article: Overexpression of circ_0034642 contributes to hypoxia-induced glycolysis, cell proliferation, migration and invasion in gliomas by facilitating TAGLN2 expression via sponging miR-625-5p

“…1,2 Despite the use of combined therapies, such as chemotherapy, radiotherapy and immunotherapy, the median survival is only 14.6 months. [3][4][5] Recurrence, high invasiveness and hypoxia have been shown to impair the therapeutic outcomes of glioma. Hypoxia was reported to stimulate angiogenesis, cell survival and metastasis in a variety of cancers, thereby increasing the aggressiveness of the cancers.…”

<p>Tanshinone IIA Suppresses Glioma Cell Proliferation, Migration and Invasion Both in vitro and in vivo Partially Through miR-16-5p/Talin-1 (TLN1) Axis</p>

“…The effect of miR-16-5p on Cyclin D1, MMP-9 and Vimentin expression was in accordance with other findings. 17,29,30 33 Bcl2 and the NF-κB1. 17 Herewith, we confirmed TLN1 to be a novel target gene of miR-16-5p in glioma.…”

“…The effect of miR-16-5p on Cyclin D1, MMP-9 and Vimentin expression was in accordance with other findings. 17 , 29 , 30 Besides, miR-16-5p had been implicated with radioresistance and chemoresistance in glioma. For example, Chaudhry et al 31 examined the miRNAs expression pattern in carcinogenesis of glioblastoma cells under ionizing radiation therapy and found that miR-16-5p was deregulated in irradiated M059J and M059K cells.…”