LncRNA PVT1 Facilitates Tumorigenesis and Progression of Glioma via Regulation of MiR-128-3p/GREM1 Axis and BMP Signaling Pathway

Abstract

The current research was aimed at probing into the role of long noncoding RNA (lncRNA) PVT1 in the pathogenesis of glioma and the regulatory mechanism of PVT1/miR-128-3p/GREM1 network in glioma via regulation of the bone morphogenetic protein (BMP) signaling pathway. Microarray analysis was used for preliminary screening for candidate lncRNAs and mRNAs in glioma tissues. Real-time quantitative polymerase chain reaction, Western blot, MTT assay, flow cytometry, migration and invasion assays, and xenograft tumor model were utilized to examine the influence of the lncRNA PVT1/miR-128-3p/GREM1 network on the biological functions of glioma cells. Luciferase assay and RNA-binding protein immunoprecipitation assay were used to validate the miR-128-3p-target relationships with lncRNA PVT1 or GREM1. In addition, the impact of GREM1 on BMP signaling pathway downstream proteins BMP2 and BMP4 was detected via Western blot. LncRNA PVT1 was highly expressed in human glioma tissues and significantly associated with WHO grade (I-II vs III-IV; p < 0.05). There existed a regulatory relationship between lncRNA PVT1 and miR-128-3p as well as that between miR-128-3p and GREM1. MiR-128-3p was downregulated, whereas GREM1 was upregulated in glioma tissues in comparison with para-carcinoma tissues. Overexpression of GREM1 promoted the proliferation and metastatic potential of glioma cells, whereas miR-128-3p mimics inhibited the glioma cell activity through targeting GREM1. Furthermore, lncRNA PVT1 acted as a sponge of miR-128-3p and, thus, influenced the BMP signaling pathway downstream proteins BMP2 and BMP4 through regulating GREM1. LncRNA PVT1 modulated GREM1 and BMP downstream signaling proteins through sponging miR-128-3p, thereby promoting tumorigenesis and progression of glioma.

Long non-coding RNA PVT1 interacts with MYC and its downstream molecules to synergistically promote tumorigenesis

“…In gliomas, PVT1 is also highly expressed. PVT1 can promote the development of glioma cells through various mechanisms, resulting in a worse prognosis for patients with glioma and high PVT1 expression [18,161,162]. Multiple meta-analyses have also shown that PVT1 can be used as a new tumor biomarker and a predictor of poor prognosis in different cancers [163][164][165][166][167].…”

“…PVT1 can also serve as a potential predictor of cancer progression and patient prognosis [10,14,15]. Most studies have reported that PVT1 can promote proliferation, angiogenesis, apoptosis escape, and participate in DNA rearrangements, which might ultimately promote carcinogenesis [7,10,11,13,17,18]. However, recent studies have shown that PVT1, also a microRNA Host gene, can encode miR-1204, miR-1205, miR-1206, miR-1207-5p, miR-1207-3p, and miR-1208 [7,[19][20][21].…”

miR‐128‐3p contributes to mitochondrial dysfunction and induces apoptosis in glioma cells via targeting pyruvate dehydrogenase kinase 1

“…Glioma is also one of the most malignant human brain tumors with high morbidity and low survival rates. Clinical therapy of glioma depends on the location, type, grade, and size of tumors, as well as the health status of the patient . Although huge progress has been achieved in surgical procedures and other adjuvant therapies for glioma, the mortality or recurrence of these glioma patients was still high.…”

“…the location, type, grade, and size of tumors, as well as the health status of the patient. 2,3 Although huge progress has been achieved in surgical procedures and other adjuvant therapies for glioma, the mortality or recurrence of these glioma patients was still high. Even managed with the most aggressive treatments including surgery, chemotherapy, and radiotherapy, the 2-year survival rate of polygenic glioblastoma, degenerative astrocytoma, and low-grade astrocytoma is only 9, 45, and 66%, respectively.…”

Long noncoding RNA SNHG17 induced by YY1 facilitates the glioma progression through targeting miR-506-3p/CTNNB1 axis to activate Wnt/β-catenin signaling pathway

“…For example, lncRNA NEAT1 drove the development of glioma through inhibiting miR-132 to enhance the expression of SOX2 [21]. LncRNA PVT1 promoted glioma tumorigenesis and progression by targeting miR-128-3p/GREM1 axis and regulating BMP signaling pathway [22]. LncRNA MALAT1 was reported to have malignant status and predicted poor prognosis in glioma [23].…”