AUTHOR=Momtazmanesh Sara , Rezaei Nima 

TITLE=Long Non-Coding RNAs in Diagnosis, Treatment, Prognosis, and Progression of Glioma: A State-of-the-Art Review

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.712786

DOI=10.3389/fonc.2021.712786

ISSN=2234-943X

ABSTRACT=<p>Glioma is the most common malignant central nervous system tumor with significant mortality and morbidity. Despite considerable advances, the exact molecular pathways involved in tumor progression are not fully elucidated, and patients commonly face a poor prognosis. Long non-coding RNAs (lncRNAs) have recently drawn extra attention for their potential roles in different types of cancer as well as non-malignant diseases. More than 200 lncRNAs have been reported to be associated with glioma. We aimed to assess the roles of the most investigated lncRNAs in different stages of tumor progression and the mediating molecular pathways in addition to their clinical applications. lncRNAs are involved in different stages of tumor formation, invasion, and progression, including regulating the cell cycle, apoptosis, autophagy, epithelial-to-mesenchymal transition, tumor stemness, angiogenesis, the integrity of the blood-tumor-brain barrier, tumor metabolism, and immunological responses. The well-known oncogenic lncRNAs, which are upregulated in glioma, are <italic>H19</italic>, <italic>HOTAIR</italic>, <italic>PVT1</italic>, <italic>UCA1</italic>, <italic>XIST</italic>, <italic>CRNDE</italic>, <italic>FOXD2-AS1</italic>, <italic>ANRIL</italic>, <italic>HOXA11-AS</italic>, <italic>TP73-AS1</italic>, and <italic>DANCR</italic>. On the other hand, <italic>MEG3</italic>, <italic>GAS5</italic>, <italic>CCASC2</italic>, and <italic>TUSC7</italic> are tumor suppressor lncRNAs, which are downregulated. While most studies reported oncogenic effects for <italic>MALAT1</italic>, <italic>TUG1</italic>, and <italic>NEAT1</italic>, there are some controversies regarding these lncRNAs. Expression levels of lncRNAs can be associated with tumor grade, survival, treatment response (chemotherapy drugs or radiotherapy), and overall prognosis. Moreover, circulatory levels of lncRNAs, such as <italic>MALAT1, H19, HOTAIR, NEAT1, TUG1, GAS5, LINK-A</italic>, and <italic>TUSC7</italic>, can provide non-invasive diagnostic and prognostic tools. Modulation of expression of lncRNAs using antisense oligonucleotides can lead to novel therapeutics. Notably, a profound understanding of the underlying molecular pathways involved in the function of lncRNAs is required to develop novel therapeutic targets. More investigations with large sample sizes and increased focus on <italic>in-vivo</italic> models are required to expand our understanding of the potential roles and application of lncRNAs in glioma.</p>