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

Sep 21, 2026

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Colorectal cancer (CRC) and gastric cancer (GC) drive substantial cancer mortality worldwide. Despite progress in molecular understanding and improved treatments, patient survival remains limited, with metastasis and drug resistance playing central roles. Long noncoding RNAs (lncRNAs) influence cancer development through epigenetic regulation and interactions with microRNAs (miRNAs) and proteins, including acting as miRNA precursors or pseudogenes. Circulating lncRNAs further provide non-invasive biomarkers for diagnosis, prognosis, and prediction of therapy response across CRC and GC. This review summarizes lncRNA roles in chemoresistance and highlights their potential as therapeutic targets.

LanguageEnglish

CategoryHealthcare

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Pages30

Reading Time1 h 16 min

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Abstract

Introduction

Oncogenic and tumor suppressor lncRNAs

Clinical and Experimental Medicine (2024) 24:29 [https://doi.org/10.1007/s10238-023-01260-5](https://doi.org/10.1007/s10238-023-01260-5) Decoding the regulatory landscape of lncRNAs as potential diagnostic and prognostic biomarkers for gastric and colorectal cancers Arefeh Zabeti Touchaei1 · Sogand Vahidi2 · Ali Akbar Samadani3 Received: 30 August 2023 / Accepted: 12 December 2023 / Published online: 31 January 2024 © The Author(s) 2024 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 modificationsand 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. * Sogand Vahidi[so.vahidii@gmail.com](so.vahidii@gmail.com) * Ali Akbar Samadani[a_a_hormoz@yahoo.com](a_a_hormoz@yahoo.com) 1 Department of Chemistry, Lahijan Branch, Islamic Azad University, Lahijan, Iran 2 Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran 3 Guilan Road Trauma Research Center, Trauma Institute, Guilan University of Medical Sciences, Rasht, Iran Graphical Abstract Keywords Long noncoding RNA (lncRNA) · Colorectal cancer · Gastric cancer · Drug resistance · Therapeutic targets Introduction Oncogenicand tumor suppressor lncRNAs The well-researched oncogenic lncRNAs have a variety of targets and contribute in various ways to the development of tumors. Numerous studies have demonstrated that these lncRNAs are much more expressed in tumor tissues when compared to normal tissues, and individuals who express these lncRNAs more frequently have poor prognoses. It has been discovered that lncRNAs interact with numerous pathways to mediate oncogenic expression, which has a substantial impact on the appearance and development of various tumor cells [1] . Colorectal cancer-associated transcript (CCAT), H19, metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), and HOX transcript antisense intergenic RNA (HOTAIR) are among them; they are the most representative lncRNAs [2] . The earliest recognized long noncoding RNAs in CRC are called CCATs, and they are found at chromosome 8q24 . The results of CCAT1 and CCAT2 showed how important lncRNAs are for CRC and stressed the demand for thorough lncRNA analysis in CRC [3] . The specific mechanism is that CCAL could cause multidrug resistance (MDR) by activating the Wnt/β-catenin signal pathway by inhibiting AP-2 and further enhancing MDR1/P express

FAQs

Why are CRC and gastric cancer still associated with poor overall survival?

Metastasis and drug resistance significantly contribute to high mortality and unsatisfactory survival despite advances in molecular research and drug treatment.

How do lncRNAs regulate gene expression in CRC and GC?

lncRNAs regulate gene expression via epigenetic modifications and by interacting with miRNAs and proteins, including roles as miRNA precursors or pseudogenes that affect transcriptional and post-transcriptional regulation.

In what ways can lncRNAs be used as biomarkers and therapeutic targets?

Circulating lncRNAs are presented as non-invasive biomarkers for diagnosis, prognosis, and predicting drug therapy response, and the review also discusses lncRNAs as potential therapeutic targets in CRC and GC.

Sep 21, 2026

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