Citation: Kciuk, M.; Yahya, E.B.; Mohamed, M.M.I.; Abdulsamad, M.A.; Allaq, A.A.; Gieleci ´ nska, A.; Kontek, R. Insights into the Role of LncRNAs and miRNAs in Glioma Progression and Their Potential as Novel Therapeutic Targets. Cancers 2023, 15, 3298. https://doi.org/ 10.3390/cancers15133298 Academic Editors: Guillermo Barreto, Marco Marcia and Bruno Charpentier Received: 29 May 2023 Revised: 19 June 2023 Accepted: 20 June 2023 Published: 22 June 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). cancers Review Insights into the Role of LncRNAs and miRNAs in Glioma Progression and Their Potential as Novel Therapeutic Targets Mateusz Kciuk 1,2, * , Esam Bashir Yahya 3, * , Montaha Mohamed Ibrahim Mohamed 4 , Muhanad A. Abdulsamad 5 , Abdulmutalib A. Allaq 6 , Adrianna Gieleci ´ nska 1,2 and Renata Kontek 1 1 Department of Molecular Biotechnology and Genetics, University of Lodz, 90-237 Lodz, Poland 2 Doctoral School of Exact and Natural Sciences, University of Lodz, 90-237 Lodz, Poland 3 Bioprocess Technology Division, School of Industrial Technology, Universiti Sains Malaysia, Penang 11800, Malaysia 4 Faculty of Applied Medical Sciences, Mohail Aseer, King Khalid University, Abha 62529, Saudi Arabia 5 Department of Molecular Biology, Faculty of Science, Sabratha University, Sabratha 00218, Libya 6 Faculty of Applied Science, Universiti Teknologi MARA, Shah Alam 40450, Malaysia * Correspondence: mateusz.kciuk@edu.uni.lodz.pl (M.K.); essam912013@gmail.com (E.B.Y.) Simple Summary: Recent research has revealed the involvement of long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs) in glioma development and advancement, suggesting their potential as biomarkers and therapeutic targets. Late-stage diagnosis and the limited effectiveness of conventional treatments contribute to poor glioma outcomes, highlighting the need for early detection methods. Advances in biotechnology and neuroscience have shed light on non-coding RNAs role in glioma angiogenesis and progression. This review explores the impact of lncRNAs and miRNAs on gene regulation, either promoting or inhibiting glioma progression and establishes connections between these crucial cancer-related molecules. Abstract: Accumulating evidence supports that both long non-coding and micro RNAs (lncRNAs and miRNAs) are implicated in glioma tumorigenesis and progression. Poor outcome of gliomas has been linked to late-stage diagnosis and mostly ineffectiveness of conventional treatment due to low knowledge about the early stage of gliomas, which are not possible to observe with conventional diagnostic approaches. The past few years witnessed a revolutionary advance in biotechnology and neuroscience with the understanding of tumor-related molecules, including non-coding RNAs that are involved in the angiogenesis and progression of glioma cells and thus are used as prognostic biomarkers as well as novel therapeutic targets. The emerging research on lncRNAs and miRNAs highlights their crucial role in glioma progression, offering new insights into the disease. These non- coding RNAs hold significant potential as novel therapeutic targets, paving the way for innovative treatment approaches against glioma. This review encompasses a comprehensive discussion about the role of lncRNAs and miRNAs in gene regulation that is responsible for the promotion or the inhibition of glioma progression and collects the existing links between these key cancer-related molecules. Keywords: glioma; long RMA; micro non-coding RNAs; gene therapy; brain tumors 1. Introduction The majority of the human genome is composed of non-protein coding genes. These genes do not code for proteins but instead produce various types of RNA molecules that are not translated into proteins [1]. For a long time, the non-translated regions of the human genome were often referred to as “junk DNA” because their function was not well understood. However, in the last two decades, advancements in genomic research have revealed that these non-coding regions play critical roles in gene regulation and other important biological processes [2]. In general, non-coding RNAs can be classified into small Cancers 2023, 15, 3298. https://doi.org/10.3390/cancers15133298 https://www.mdpi.com/journal/cancers