Identification of novel LncRNA targeting Smad2/PKCα signal pathway to negatively regulate malignant progression of glioblastoma

Abstract

Glioblastoma multiforme (GBM) is a highly proliferative cancer with generally poor prognosis and accumulating evidence has highlighted the potential of long noncoding RNAs (lncRNAs) in the biological behaviors of glioma cells. This study focused on the identification of lncRNAs to identify targets for possible GBM prognosis. Microarray expression profiling found that 1,759 lncRNAs and 3,026 messenger RNAs (mRNAs) were upregulated, and 1932s lncRNA and 2,979 mRNAs were downregulated in GBM. Bioinformatics analysis and experimental verification identified TCONS_00020456 (TCON) for further analysis. In situ hybridization, along with immunohistochemical and receiver operating characteristic analysis determined TCON (truncation value = 3.5) as highly sensitive and specific in GBM. Grade IV patients with glioma life span with different lncRNA staining scores were analyzed. TCON staining scores below 3.5 indicated poor prognosis (life span ranging from 0.25 to 7 months), even if the glioma was surgically removed. TCON decreased significantly in GBM, and showed a coexpressional relationship with Smad2 and protein kinase C α (PKCα). Overexpression of TCON reduced the proliferation on one hand and migration, invasion on the other. TCON also inhibited epithelial–mesenchymal transformation and glioma progression in vivo, based on a nude mouse tumorigenicity assay. In addition, we predicted a potential binding site and intersection that microRNAs targeting Smad2, PKCα, and TCON through RACE pretest and bioinformatics analysis. Taken together, TCON, regarded as oncosuppressor, targeting the Smad2/PKCα axis plays a novel role in inhibiting the malignant progression of glioma. Moreover, it also demonstrates that the level of TCON can be used as a prognostic and diagnostic biomarker for GBM.

The transcription factor USF1 promotes glioma cell invasion and migration by activating lncRNA HAS2-AS1

“…In recent years, more and more studies have focused on lncRNAs as tumor diagnostic markers and potential therapeutic targets. Numerous researches have shown that lncRNAs play an important regulatory role in the development of various cancers, including glioma [3][4][5]. For example, linc00319 expresses at a high level in glioma and is significantly associated with poor prognosis of glioma patients, while knockdown of linc00319 impairs cell proliferation, arrests cell cycle and induces cell apoptosis of glioma cells [6].…”

Roles of Long Noncoding RNAs in Conferring Glioma Progression and Treatment

“…Li et al showed that LINC00645 could promote EMT, which was indispensable in the invasion and migration of glioma cells involving TGF-b by regulating the miR-205-3p-ZEB1 axis; thus, LINC00645 could be a prognostic indicator for glioma (57). A novel lncRNA-TOCN that targets the Smad2/PKCa signaling pathway to inhibit malignant progression of glioma was highlighted by Tang et al and could serve as a prognostic indicator of GBM (58). The expression of multiple lncRNAs has been documented to correlate with the malignancy of gliomas and to be involved in their malignant progression, providing powerful theoretical evidence for their application as diagnostic and prognostic markers.…”

Comprehensive biological function analysis of lncRNAs in hepatocellular carcinoma

“…In the initial stage of lncRNA research, some scholars suggested that there is a difference in the expression of lncRNAs between tumor tissues and adjacent normal tissues. An increasing number of studies 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 have shown that lncRNAs may play an important biological role in the regulation of cancer development, as the biological function of lncRNAs in carcinomas is to promote cancer cell proliferation and invasion, suppress cancer cell proliferation and invasion, estimate the prognosis and efficacy, and act as potential biomarkers, as summarized in Table 1 .…”