Dataset Information

Linc00475 promotes the progression of glioma by regulating the miR-141-3p/YAP1 axis.

ABSTRACT: Glioma is the most prevalent and lethal primary brain tumour. Abundant long non-coding RNAs ( lncRNAs) are aberrant and play crucial roles in the oncogenesis of glioma. The exact functions of linc00475 in glioma remain blurred. Here, we analysed the expression levels of linc00475 by qRT-PCR and discovered that linc00475 was up-regulated in glioma and predicted a poor prognosis in patients with glioma. Besides, inhibiting linc00475 restrained the progression of glioma in vitro and in vivo. Further experiments confirmed that linc00475 regulated the progression of glioma by acting as a sponge for miR-141-3p. Moreover, we detected the binding sites of linc00475 and miR-141-3p, the YAP1- 3'UTR and miR-141-3p by luciferase reporters. The rescue assays confirmed that inhibiting linc00475 restrained the progression of glioma through the miR-141-3p/YAP1 pathway. Collectively, our research demonstrates the key roles of linc00475 in glioma, which could be a promising therapeutic target.

SUBMITTER: Yu M

PROVIDER: S-EPMC7810941 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Linc00475 promotes the progression of glioma by regulating the miR-141-3p/YAP1 axis.

Yu Mingjun M Yi Bolong B Zhou Wen W Gong Wei W Li Gang G Yu Shijia S

Journal of cellular and molecular medicine 20201218 1

Glioma is the most prevalent and lethal primary brain tumour. Abundant long non-coding RNAs ( lncRNAs) are aberrant and play crucial roles in the oncogenesis of glioma. The exact functions of linc00475 in glioma remain blurred. Here, we analysed the expression levels of linc00475 by qRT-PCR and discovered that linc00475 was up-regulated in glioma and predicted a poor prognosis in patients with glioma. Besides, inhibiting linc00475 restrained the progression of glioma in vitro and in vivo. Furthe ...[more]

PMID: 33336871

Similar Datasets

Project description:Rationale: Glioma is the most common primary malignant tumor of human central nervous system, and its rich vascular characteristics make anti-angiogenic therapy become a therapeutic hotspot. However, the existence of glioma VM makes the anti-angiogenic therapy ineffective. SUMOylation is a post-translational modification that affects cell tumorigenicity by regulating the expression and activity of substrate proteins. Methods: The binding and modification of IGF2BP2 and SUMO1 were identified using Ni2+-NTA agarose bead pull-down assays, CO-IP and western blot; and in vitro SUMOylation assays combined with immunoprecipitation and immunofluorescence staining were performed to explore the detail affects and regulations of the SUMOylation on IGF2BP2. RT-PCR and western blot were used to detect the expression levels of IGF2BP2, OIP5-AS1, and miR-495-3p in glioma tissues and cell lines. CCK-8 assays, cell transwell assays, and three-dimensional cell culture methods were used for evaluating the function of IGF2BP2, OIP5-AS1, miR-495-3p, HIF1A and MMP14 in biological behaviors of glioma cells. Meantime, RIP and luciferase reporter assays were used for inquiring into the interactions among IGF2BP2, OIP5-AS1, miR-495-3p, HIF1A and MMP14. Eventually, the tumor xenografts in nude mice further as certained the effects of IGF2BP2 SUMOylation on glioma cells. Results: This study proved that IGF2BP2 mainly binds to SUMO1 and was SUMOylated at the lysine residues K497, K505 and K509 sites, which can be reduced by SENP1. SUMOylation increased IGF2BP2 protein expression and blocked its degradation through ubiquitin-proteasome pathway, thereby increasing its stability. The expressions of IGF2BP2 and OIP5-AS1 were up-regulated and the expression of miR-495-3p was down-regulated in both glioma tissues and cells. IGF2BP2 enhances the stability of OIP5-AS1, thereby increasing the binding of OIP5-AS1 to miR-495-3p, weakening the binding of miR-495-3p to the 3'UTR of HIF1A and MMP14 mRNA, and ultimately promoting the formation of VM in glioma. Conclusions: This study first revealed that SUMOylation of IGF2BP2 regulated OIP5-AS1/miR-495-3p axis to promote VM formation in glioma cells and xenografts growth in nude mice, providing a new idea for molecular targeted therapy of glioma.

Project description:Ovarian cancer (OC), the third common gynecologic malignancy, contributes to the most cancer-caused mortality in women. However, 70% of patients with OC are diagnosed at an advanced stage, of which the 5-year survival is less than 30%. Long noncoding RNAs (long ncRNAs or lncRNA), a type of RNA with exceeding 200 nucleotides in length but no protein-coding capability, have been demonstrated to involve the pathogenesis of various cancers and show considerable potential in the diagnosis of OC. In this study, we found that the LINC00909 expression in tumor and serum specimens of OC patients was elevated, determined by real-time quantitative, and droplet digital PCR. In receiver operating characteristic (ROC) analysis, our results revealed that serum LINC00909 distinguished cancers from normal ovarian tissue with 87.8% of sensitivity and 69.6% of specificity (AUC, 81.2%) and distinguished serous ovarian cancer from normal ovarian tissue with 90.0% of sensitivity and 75.9% of specificity (AUC, 84.5%). Furthermore, we observed that the tumor and serum LINC00909 level was positively associated with the International Federation of Gynecology and Obstetrics (FIGO) stage and the Eastern Cooperative Oncology Group (ECOG) score (reflecting patients' performance status). Also, patients with low serum LINC00909 level showed a longer overall (hazard ratio, HR = 1.874, p = 0.0004) and progression-free (HR = 1.656, p = 0.0017) survival. Functional assays indicated that the elevation of LINC00909 expression contributes to cell proliferation, migration, and invasion capability of ovarian cancer cells. Besides, we demonstrated that LINC00909 functions as a competing endogenous RNA (ceRNA) of MRC2 mRNA by sponging miR-23-3p, and thereby promotes epithelial-to-mesenchymal transition (EMT) of ovarian cancer cells. Therefore, we highlight that the LINC00909/miR-23b-3p/MRC2 axis is implicated in the pathogenesis of ovarian cancer, and serum LINC00909 may be a promising biomarker for the diagnosis of OC.

Dataset Information

Linc00475 promotes the progression of glioma by regulating the miR-141-3p/YAP1 axis.

Publications

Linc00475 promotes the progression of glioma by regulating the miR-141-3p/YAP1 axis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets