Decoding the regulatory landscape of lncRNAs as potential diagnostic and prognostic biomarkers for gastric and colorectal cancers

Abstract

Colorectal cancer (CRC) and gastric cancer (GC) are major contributors to cancer-related mortality worldwide. Despite advancements in understanding molecular mechanisms and improved drug treatments, the overall survival rate for patients remains unsatisfactory. Metastasis and drug resistance are major challenges contributing to the high mortality rate in both CRC and GC. Recent research has shed light on the role of long noncoding RNAs (lncRNAs) in the development and progression of these cancers. LncRNAs regulate gene expression through various mechanisms, including epigenetic modifications and interactions with microRNAs (miRNAs) and proteins. They can serve as miRNA precursors or pseudogenes, modulating gene expression at transcriptional and post-transcriptional levels. Additionally, circulating lncRNAs have emerged as non-invasive biomarkers for the diagnosis, prognosis, and prediction of drug therapy response in CRC and GC. This review explores the intricate relationship between lncRNAs and CRC/GC, encompassing their roles in cancer development, progression, and chemoresistance. Furthermore, it discusses the potential of lncRNAs as therapeutic targets in these malignancies. The interplay between lncRNAs, miRNAs, and tumor microenvironment is also highlighted, emphasizing their impact on the complexity of cancer biology. Understanding the regulatory landscape and molecular mechanisms governed by lncRNAs in CRC and GC is crucial for the development of effective diagnostic and prognostic biomarkers, as well as novel therapeutic strategies. This review provides a comprehensive overview of the current knowledge and paves the way for further exploration of lncRNAs as key players in the management of CRC and GC.

Keywords: Colorectal cancer; Drug resistance; Gastric cancer; Long noncoding RNA (lncRNA); Therapeutic targets.

Fig. 1

LincRNA HOTAIR regulation and function in GC and CRC

Fig. 2

LncRNAs function in GC and CRC. In the nucleus, lncRNAs participate in epigenetic modifications including histone modifications (histone acetylation, histone methylation, histone demethylation), chromatin remodeling, DNA methylations, and splicing modulations of mRNAs. In the cytoplasm, lncRNAs can interact with RNAs including miRNA sponges and regulate translation. Moreover, lncRNAs bind to proteins consisting of modulation of protein activity, protein localization, and structural and organization function

Fig. 3

LncRNAs regulate drug resistance in gastric and colorectal cancer