The Mechanism of Long Non-coding RNA in Cancer Radioresistance/Radiosensitivity: A Systematic Review

Abstract

Background and purpose: Radioresistance remains a significant challenge in tumor therapy. This systematic review aims to demonstrate the role of long non-coding RNA (lncRNA) in cancer radioresistance/radiosensitivity.Material and methods: The electronic databases Pubmed, Embase, and Google Scholar were searched from January 2000 to December 2021 to identify studies addressing the mechanisms of lncRNAs in tumor radioresistance/sensitivity, each of which required both in vivo and in vitro experiments.Results: Among the 87 studies identified, lncRNAs were implicated in tumor radioresistance/sensitivity mainly in three paradigms. 1) lncRNAs act on microRNA (miRNA) by means of a sponge, and their downstream signals include some specific molecular biological processes (DNA repair and chromosome stabilization, mRNA or protein stabilization, cell cycle and proliferation, apoptosis-related pathways, autophagy-related pathways, epithelial-mesenchymal transition (EMT), cellular energy metabolism) and some signaling mediators (transcription factors, kinases, some important signal transduction pathways) that regulate various biological processes. 2) lncRNAs directly interact with proteins, affecting the cell cycle and autophagy to contribute to tumor radioresistance. 3) lncRNAs act like transcription factors to initiate downstream signaling pathways and participate in tumor radioresistance.Conclusion: lncRNAs are important regulators involved in tumor radioresistance\sensitivity. Different lncRNAs may participate in the radioresistance with the same regulatory paradigm, and the same lncRNAs may also participate in the radioresistance in different ways. Future research should focus more on comprehensively characterizing the mechanisms of lncRNAs in tumor radioresistance to help us identify corresponding novel biomarkers and develop new lncRNA-based methods to improve radioresistance.

LINC02323 facilitates development of lung squamous cell carcinoma by miRNA sponge and RBP dysregulation and links to poor prognosis

“…LncRNAs can act as sponges to regulate gene expression by competitively binding miRNAs. 19 LINC02323 as an oncogenic gene has been found in some studies, and it is linked to numerous malignancies, such as ovarian cancer, liver cancer, and LUAD. 20 Recent evidence showed that LINC02323 upregulates E2F1 expression by competitively binding to miR‐29c‐3p, thereby changing the immune microenvironment and chemoresistance in hepatocellular carcinoma (HCC).…”

“…LncRNAs can act as sponges to regulate gene expression by competitively binding miRNAs 19 . LINC02323 as an oncogenic gene has been found in some studies, and it is linked to numerous malignancies, such as ovarian cancer, liver cancer, and LUAD 20 .…”

Biological Mechanisms to Reduce Radioresistance and Increase the Efficacy of Radiotherapy: State of the Art

“…However, the genetic and epigenetic scenario in radioresistant tumors is complicated to describe since, on the one hand, genetic and epigenetic signatures drive tumorigenesis, and on the other hand, RT itself can trigger long-term genetic and epigenetic changes in cancer cells that, in turn, affect radioresistance. Few studies have analyzed the role of ncRNAs in radioresistance and the metabolic phenotypes of radioresistant cancer cells [ 94 , 95 ]. While differentially expressed genes and ncRNAs following IR have been identified in numerous tumors, what is still little known is the relationship between specific genes/ncRNAs and radioresistance.…”

“…HIF-1α stability increases during cyclic hypoxia compared with chronic hypoxia, whereas HIF-1β is insensitive to variations in oxygen levels, as recently found in Saxena and Jolly [ 116 ]. Once activated HIF-1 triggers a transcriptional pathway of hundreds of genes—including those of glucose metabolism, cell cycle regulation and proliferation, apoptosis, immune response, the protection of tumor blood vessels, and angiogenesis [ 94 , 125 , 126 , 127 , 128 ]—which ultimately allow for the cellular adaptive response to hypoxia [ 125 ]. This consists of the formation of new blood vessels [ 126 ], a shift to anaerobic metabolism for cellular energy production, increased apoptosis, and increased myeloid cell migration in inflamed areas [ 129 ].…”

Comprehensive landscape and future perspectives of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC): Based on a bibliometric analysis

“…Long noncoding RNA (lncRNA) is a type of RNA with a length of more than 200 nucleotides. Although many lncRNAs do not directly encode proteins, it participates in various biological processes, such as chromatin remodeling, transcriptional activation, transcriptional interference, RNA processing [ [8] , [9] , [10] , [11] ]. They play a role in the development and occurrence of CRC by acting as tumor suppressor genes and oncogenes, or interacting with DNA, RNA, and proteins [ 12 , 13 ].…”