# The Role of LncRNAs in Radio- and Chemoresistance of Glioblastoma: Prognostic or Therapeutic?

## TL;DR

This review explores how long non-coding RNAs (lncRNAs) contribute to therapy resistance in glioblastoma and their potential as biomarkers or treatment targets.

## Contribution

The paper emphasizes the novel role of lncRNAs in transitioning from epigenetic to genetic resistance mechanisms in brain cancer.

## Key findings

- lncRNAs modulate gene expression and signaling pathways, contributing to therapy resistance in glioblastoma.
- lncRNAs are deregulated in tumors and show promise as prognostic biomarkers and therapeutic targets.
- Understanding lncRNA functions could improve early diagnosis and treatment outcomes in brain cancer.

## Abstract

This review highlights the role of lncRNAs in tumor progression and therapy resistance, focusing particularly on their ability to drive the transition from reversible epigenetic adaptations to stable genetic changes in resistant cancer cells. lncRNAs not only modulate gene expression and signaling pathways through interacting with miRNAs, DNA, RNA, and proteins, but also actively contribute to the reprogramming of the cellular environment. This action facilitates the shift from early adaptive, often transient, epigenetic mechanisms of resistance to more permanent genetic alterations that support tumor evolution and sustained therapy resistance. Their widespread expression and deregulation in tumors suggest their strong potential as prognostic biomarkers and as therapeutic targets, especially in combination with traditional or next-generation treatments.

Malignant brain tumors remain highly challenging to treat due to intrinsic and acquired therapy resistance and limited therapeutic options, consequently contributing to poor prognosis. Advancing the understanding of resistance mechanisms alongside novel treatment strategies is essential to improve clinical outcomes. Altered gene expression is common in tumors, and a specific class of non-coding RNAs, particularly long non-coding RNAs (lncRNAs), is frequently deregulated. LncRNAs play critical roles in processes such as cell proliferation, cell cycle arrest, and metastasis in brain cancer, functioning either as tumor promoters or suppressors. They exert their effects through transcriptional and post-transcriptional regulatory mechanisms. Understanding the functional roles of lncRNAs in malignant brain tumors has become a priority, as they are differentially expressed in tumors compared to healthy tissue. These molecules are studied for their potential as therapeutic targets and biomarkers in oncology. This review provides an overview of current research on brain cancer and lncRNAs, emphasizing the need for further investigation into their specific roles in therapy resistance and their involvement in various pathways. A better understanding of lncRNAs and their role in brain cancer could offer valuable insights into their prognostic and therapeutic potential, with the promise of improving early diagnosis and treatment outcomes.