lncRNA PDCD4-AS1 Promotes the Progression of Glioma by Regulating miR-30b-3p/METTL7B Signaling

Abstract

Background. Gliomas are the most common and most malignant primary tumors of the adult central nervous system, but their etiology and pathogenesis remain unclear. This study was aimed at investigating the expression and function of lncRNA PDCD4-AS1 in glioma and elucidating the mechanism by which PDCD4-AS1 regulates the biological features of glioma. Method. The expression of PDCD4-AS1 was determined by bioinformatic analysis and qRT-PCR assay. PDCD4-AS1 was knocked down in glioma cells using siRNA transfection. The functional analysis of cells was conducted using CCK-8 proliferation, cell migration, and invasion assays, as well as cell cycle analysis. An in vivo tumorigenesis assay was performed to investigate the role of PDCD4-AS1 knockdown in glioma tumor growth. We performed bioinformatic analysis, RNA pull-down, and luciferase reporter assays to investigate the downstream targets of PDCD4-AS1. A rescue experiment was then performed to confirm the regulating mechanism. Results. PDCD4-AS1 was found to be significantly upregulated in glioma patients’ tumor tissues and cell lines. The silencing of PDCD4-AS1 inhibited glioma cell proliferation, invasion, migration, and induced cell cycle arrest. In vivo experiments showed that silencing PDCD4-AS1 inhibited glioma tumor growth. An investigation of the underlying mechanism suggested that PDCD4-AS1 positively regulated METTL7B expression by sponging miR-30b-3. Both the knockdown of miR-30b-3p and the overexpression of METTL7B could, respectively, reverse the malignant phenotype of cells affected by silencing PDCD4-AS1. Conclusion. These results demonstrate that PDCD4-AS1 exerted an oncogenic role by regulating the miR-30b-3p/METTL7B axis.

The role and clinical relevance of long non-coding RNAs in glioma

“…Lastly, ADAMTS9-AS2, which is downregulated in glioblastoma and correlates with glioma grading, has been shown to inhibit cell migration and invasion upon overexpression [ 55 , 56 ]. Numerous studies are currently underway to develop a potential therapeutic approach based on interactions between lncRNAs and miRNAs, which reveal the vital role of this interaction in proliferation, angiogenesis, invasion, metastasis, cell survival and resistance to therapy in glioma ( Table 1 ) [ [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] ].…”

“… LncRNAs Expression of lncRNAs miRNAs Targets Function Ref. HOXA11-AS Up let-7b-5p Tpl2-MEK1/2-ERK1/2 axis Sensitizes glioblastoma cells to ROS, drastically impairing tumor growth and prolonging survival of mouses [ 57 ] MIR210HG Down miR-377–3p LMX1A Suppresses glioma cell proliferation [ 58 ] PDCD4-AS1 Down miR-30b-3p METTL7B Inhibits glioma cell proliferation, invasion, migration, and induces cell cycle arrest [ 59 ] GSCAR Down miR-6760–5p SRSF1 Promotes tumor cell responses to TMZ [ 60 ] SPRY4-IT1 Down miR-101–3p EZH2 and VEGFA Achieves cell proliferation and angiogenesis [ 61 ] LINC01018 Up miR-942–5p KNG1 Suppresses the migration, invasion, and proliferation of glioma cells [ 62 ] LINC01018 Up miR-182–5p ADRA2C, RAB6B, RAB27B, RAPGEF5, STEAP2, TAGLN3, and UNC13C Inhibits cell proliferation and metastasis [ 63 ] TUSC7 Up miR-10a-5p BDNF/ERK axis Suppre...…”