LncRNA LINC01018/miR‐942‐5p/KNG1 axis regulates the malignant development of glioma in vitro and in vivo

Abstract

Aims Since the inhibitory effect of KNG1 on glioma has been proved, this study further explores the regulation of the lncRNA/miRNA axis on KNG1 in glioma. Methods The miRNAs that target KNG1 and the lncRNA that targets miR‐942‐5p were predicted by bioinformatics analysis and verified by experiments. The correlations between miR‐942‐5p and the survival of patients and between KNG1 and miR‐942‐5p were analyzed. After transfection, cell migration, invasion, proliferation, and cell cycle were detected through wound healing, Transwell, colony formation, and flow cytometry assays. A mouse subcutaneous xenotransplanted tumor model was established. The expressions of miR‐942‐5p, KNG1, LINC01018, and related genes were evaluated by quantitative real‐time reverse transcription polymerase chain reaction (RT‐qPCR), Western blot, or immunohistochemistry. Results MiR‐942‐5p targeted KNG1, and LINC01018 sponged miR‐942‐5p. The high survival rate of patients was related to low miR‐942‐5p level. MiR‐942‐5p was highly expressed, whereas KNG1 was lowly expressed in glioma. MiR‐942‐5p was negatively correlated with KNG1. Silent LINC01018 or KNG1 and miR‐942‐5p mimic enhanced the migration, invasion, and proliferation of glioma cells, and regulated the expressions of metastasis‐related and proliferation‐related genes. LINC01018 knockdown and miR‐942‐5p mimic promoted glioma tumor growth in mice. The levels of miR‐942‐5p and KNG1 were decreased by LINC01018 knockdown, and LINC01018 expression was suppressed by miR‐942‐5p mimic. MiR‐942‐5p inhibitor, KNG1, and LINC01018 had the opposite effect to miR‐942‐5p mimic. Conclusion LINC01018/miR‐942‐5p/KNG1 pathway regulates the development of glioma cells in vitro and in vivo.

Research progress on function and mechanism of long non-coding RNA in glioma

“…LncRNA PSMB8-AS1 competitively binds with miR-382-3p, enhancing the expression of BCAT1, thereby promoting the in vitro proliferation and migration of glioma cells, inhibiting apoptosis, and stimulating the in vitro growth of transplanted tumors [15]. LncRNA LINC01018 acts as a sponge for miR-942-5p, selectively inhibiting KNG1, and enhancing the proliferation, invasion, and migration abilities of glioma cells [16]. The growth and metastatic capabilities of tumors depend on neovascularization, providing sufficient oxygen, nutrients, and waste removal to maintain metabolism and survival.…”

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...…”

LncRNA LINC01018 Screens Type 2 Diabetes Mellitus and Regulates β Cell Function Through Modulating miR-499a-5p

“…lncRNA LINC01018 was also found to be dysregulated in the constructed expression profile, but whether it was involved in T2DM development is unknown [14]. The dysregulation of LINC01018 in other diseases was demonstrated to regulate the malignancy of tumors and the progression of cells [15][16][17][18]. Therefore, the dysregulation of LINC01018 in T2DM was also speculated to play roles in disease pathogenesis and development.…”