An RBM10 and NF-κB interacting host lncRNA promotes JEV replication and neuronal cell death.

IMPORTANCE: Central nervous system infection by flaviviruses such as Japanese encephalitis virus, Dengue virus, and West Nile virus results in neuroinflammation and neuronal damage. However, little is known about the role of long non-coding RNAs (lncRNAs) in flavivirus-induced neuroinflammation and neuronal cell death. Here, we characterized the role of a flavivirus-induced lncRNA named JINR1 during the infection of neuronal cells. Depletion of JINR1 during virus infection reduces viral replication and cell death. An increase in GRP78 expression by JINR1 is responsible for promoting virus replication. Flavivirus infection induces the expression of a cellular protein RBM10, which interacts with JINR1. RBM10 and JINR1 promote the proinflammatory transcription factor NF-κB activity, which is detrimental to cell survival.

Role of Non-Coding RNAs in TGF-ß Signalling in Glioma.

Brain tumours and Gliomas, in particular, are among the primary causes of cancer mortality worldwide. Glioma diagnosis and therapy have not significantly improved despite decades of efforts. Autocrine TGF-ß signalling promotes glioma proliferation, invasion, epithelial-to-mesenchymal transition (EMT), and drug resistance. Non-coding RNAs such as miRNA, lncRNA, and circRNAs have emerged as critical transcriptional and post-transcriptional regulators of TGF-ß pathway components in glioma. Here, we summarize the complex regulatory network among regulatory ncRNAs and TGF-ß pathway during Glioma pathogenesis and discuss their role as potential therapeutic targets for Gliomas.

Emerging role of transforming growth factor-ß-regulated long non-coding RNAs in prostate cancer pathogenesis.

Prostate cancer (PCa) is the most common malignancy in men. Despite aggressive therapy involving surgery and hormonal treatments, the recurrence and emergence of metastatic castration-resistant prostate cancer (CRPCa) remain a major challenge. Dysregulation of the transforming growth factor-ß (TGF-ß) signaling pathway is crucial to PCa development and progression. This also contributes to androgen receptor activation and the emergence of CRPC. In addition, TGF-ß signaling regulates long non-coding RNA (lncRNA) expression in multiple cancers, including PCa. Here, we discuss the complex regulatory network of lncRNAs and TGF-ß signaling in PCa and their potential applications in diagnosing, prognosis, and treating PCa. Further investigations on the role of lncRNAs in the TGF-ß pathway will help to better understand PCa pathogenesis.

LINC01711 promotes transforming growth factor-beta (TGF-ß) induced invasion in glioblastoma multiforme (GBM) by acting as a competing endogenous RNA for miR-34a and promoting ZEB1 expression.

GBM is the central nervous system's most aggressive and malignant tumor. TGF-ß expression is elevated in GBM, and it promotes invasion and EMT. TGF-ß regulates the expression of several lncRNAs, which promote glioma pathogenesis. Here we characterize the role of TGF-ß-induced lncRNA- LINC01711 in glioma pathogenesis. We show that LINC01711 expression is significantly upregulated in GBM tissues and is associated with poor overall survival of GBM patients. Loss-of-function studies illustrate that LINC01711 promotes proliferation, migration, and invasion in GBM. In addition, LINC01711 depletion sensitizes glioma cells to Temozolomide (TMZ) induced apoptosis by inhibiting ZEB1 expression. LINC01711 functions as a competing endogenous RNA for miR-34a and promotes ZEB1 expression to regulate invasion. Our findings suggest that LINC01711 is an attractive therapeutic target for GBM.

Transforming Growth Factor-Beta-Regulated LncRNA-MUF Promotes Invasion by Modulating the miR-34a Snail1 Axis in Glioblastoma Multiforme.

Transforming growth factor beta (TGF-ß)-regulated long-non-coding RNAs (lncRNAs) modulate several aspects of tumor development such as proliferation, invasion, metastasis, epithelial to mesenchymal transition (EMT), and drug resistance in various cancers, including Glioblastoma multiforme (GBM). We identified several novel differentially expressed lncRNAs upon TGF-ß treatment in glioma cells using genome-wide microarray screening. We show that TGF-ß induces lncRNA-MUF in glioma cells, and its expression is significantly upregulated in glioma tissues and is associated with poor overall survival of GBM patients. Knockdown of lncRNA-MUF reduces proliferation, migration, and invasion in glioma cells and sensitizes them to temozolomide (TMZ)-induced apoptosis. In addition, lncRNA-MUF downregulation impairs TGF-ß-induced smad2/3 phosphorylation. In line with its role in regulating invasion, lncRNA-MUF functions as a competing endogenous RNA (ceRNA) for miR-34a and promotes Snail1 expression. Collectively, our findings suggest lncRNA-MUF as an attractive therapeutic target for GBM.

The Expanding Regulatory Mechanisms and Cellular Functions of Long Non-coding RNAs (lncRNAs) in Neuroinflammation.

LncRNAs have emerged as important regulatory molecules in biological processes. They serve as regulators of gene expression pathways through interactions with proteins, RNA, and DNA. LncRNA expression is altered in several diseases of the central nervous system (CNS), such as neurodegenerative disorders, stroke, trauma, and infection. More recently, it has become clear that lncRNAs contribute to regulating both pro-inflammatory and anti-inflammatory pathways in the CNS. In this review, we discuss the molecular pathways involved in the expression of lncRNAs, their role and mechanism of action during gene regulation, cellular functions, and use of lncRNAs as therapeutic targets during neuroinflammation in CNS disorders.