LncRNA TCONS_00004099-derived microRNA regulates oncogenesis through PTPRF in gliomas

Glioblastoma is the most common and aggressive primary tumor in the central nervous system (CNS). Patients with glioblastomas have poor prognosis due to its aggressive clinical behavior and resistance to the chemotherapeutic agent temozolomide (TMZ). Aberrant long non-coding RNAs (lncRNAs) are involved in glioma progression and its regulatory mechanisms. Analysis of sequencing data identified a new lncRNA, named lncRNA TCONS_00004099, which could derive a new microRNA and was highly expressed in glioma.

To elucidate the role of lncRNA TCONS_00004099 in gliomas, Quantitative Real-time PCR (qPCR) was used to assess the differential expression of lncRNA TCONS_00004099 and its related miRNA in glioma tissues, normal brain tissues, glioma cell lines (U87 and U251 cells), and a normal human embryonic brain cell line (HEB). Cell Counting Kit-8 (CCK8) assays to assess cell proliferation, flow cytometry assays examining apoptosis and the cell cycle, colony formation assays, wound healing assay, transwell assays, and zebrafish xenograft models were performed to further clarify the effects of the lncRNA and the related miRNA. Finally, Western blots were carried out to verify the mechanisms related to PTPRF (Protein Tyrosine Phosphatase Receptor Type F).

LncRNA TCONS_00004099 was significantly increased in glioma tissues and glioma cell lines. A novel miRNA (miRNA TCONS_00004099) derived from the lncRNA was identified by qPCR. Knockdown of this lncRNA suppressed cell proliferation, migration, invasion and enhanced TMZ-induced apoptosis in U87 and U251 cell lines in vitro and in vivo. The miRNA mimics or inhibitor of miRNA TCONS_00004099 was used to reverse the effects of knockdown or overexpression of lncRNA TCONS_00004099, respectively. Western Blot analyses verified that PTPRF is one of the downstream targets of lncRNA TCONS_00004099.

These results demonstrated that lncRNA TCONS_00004099 promoted malignant behaviors in gliomas, including proliferation, metastasis, and anti-apoptosis. The effect of lncRNA TCONS_00004099 was mediated through miRNA TCONS_00004099 and its target PTPRF. Thus, the lncRNA TCONS_00004099/miRNA/PTPRF axis may be a potential therapeutic target for gliomas.