HNRNPD interacts with ZHX2 regulating the vasculogenic mimicry formation of glioma cells via linc00707/miR-651-3p/SP2 axis

Abstract

Studies have found that RNA-binding proteins (RBPs) are dysfunctional and play a significant regulatory role in the development of glioma. Based on The Cancer Genome Atlas database and the previous studies, we selected heterogeneous nuclear ribonucleoprotein (HNRNPD) as the research candidate and sought its downstream targeted genes. In the present study, HNRNPD, linc00707, and specific protein 2 (SP2) were highly expressed, while zinc fingers and homeboxes 2 (ZHX2) and miR-651-3p were remarkedly downregulated in glioma tissues and cells. HNRNPD, linc00707, and SP2 knockdown or ZHX2 and miR-651-3p overexpression suppressed glioma cells proliferation, migration, and invasion and vasculogenic mimicry (VM) formation. Knockdown of HNRNPD increased the stability of ZHX2 mRNA. ZHX2 bound to the promoter region of linc00707 and negatively regulate its expression. Linc00707 could bind with miR-651-3p, while miR-651-3p bound to the 3′ untranslated region (3′UTR) of SP2 mRNA to negatively regulate its expression. The transcription factor SP2 directly bound to the promoter regions of the VM formation-related proteins MMP2, MMP9, and VE-cadherin, playing a role in promoting transcription in order to regulate the VM formation ability of glioma cells.

miR-651-3p Enhances the Sensitivity of Hepatocellular Carcinoma to Cisplatin via Targeting ATG3-Mediated Cell Autophagy

“…This study proved that miR-651-3p downregulation was related to the resistance of HCC cells to CDDP. Decreased miR-651-3p has been found in gastric cancer, and the proliferation and migration of the tumor cells can be effectively inhibited when miR-651-3p is overexpressed [ 13 ]. Therefore, it was hypothesized in this study that miR-651-3p involved the progression of HCC.…”

“…For instance, miR-124 downregulation is related to the stem formation and sorafenib resistance of HCC cells [ 12 ]. A previous study has identified miR-651-3p as a tumor inhibitor that can effectively suppress the progression of glioma cancer [ 13 ]. However, the role of miR-651-3p in HCC remains unclear.…”

LncRNA GACAT3: A Promising Biomarker and Therapeutic Target in Human Cancers

“…Although gliomas are relatively rare, they are aggressive tumors with high morbidity and mortality rates ( Ostrom et al, 2014 ). LncRNAs are aberrantly expressed in glioma tissues and cell lines and are thought to affect the occurrence and development of the tumor ( Peng et al, 2018 ; Yu et al, 2021 ). Recent studies have shown that GACAT3 is overexpressed in glioma tissues and is incrementally elevated during disease progression.…”

Review of LINC00707: A Novel LncRNA and Promising Biomarker for Human Diseases

“…LINC00707 is upregulated in disease such as lung cancer (Ma et al, 2018;Zhang et al, 2019;Shao et al, 2021), pneumonia (Zou et al, 2021), melanoma (Yang et al, 2018), colorectal cancer (CRC) (Shao et al, 2019;Zhu H. et al, 2019;Wang et al, 2020), glioma (Liu and Hu, 2020;Yu et al, 2021), clear cell renal cell carcinoma (Pang et al, 2020), breast cancer (BC) (Jiang et al, 2020;Yuan et al, 2020), osteosarcoma (Zhang et al, 2021), cervical cancer (Guo et al, 2021), bladder cancer (Gao and Ji, 2021), ovarian cancer (Guo et al, 2021), gastric cancer (Xie et al, 2019), hepatocellular carcinoma (Tu et al, 2019;Wang et al, 2019), and SCI (Zhu S. et al, 2019). LINC00707 dysregulation contributes to the process of osteogenic differentiation (Jia et al, 2019;Cai et al, 2020;Liu J. et al, 2020) of HBMSCs.…”

“…LINC00707 is overexpressed in glioma tissues (Liu and Hu, 2020;Yu et al, 2021) and cells. This high expression is associated with poor glioma clinicopathological parameters, including Karnofsky performance status score and WHO grade (Liu and Hu, 2020).…”