The lncrnas: innovative multifunctional players of drug resistance in colorectal cancer

Hossein Maghsoudi; Motahareh Rasoulzadeh; Maryam Abbastabar; Ahmad Fazilat; Farhad Sheikhnia; Bita Azizzadeh; Mohamad Valilo; Maryam Majidinia

doi:10.1186/s12935-025-03951-3

The lncrnas: innovative multifunctional players of drug resistance in colorectal cancer

Cancer Cell Int. 2025 Nov 23;25(1):442. doi: 10.1186/s12935-025-03951-3.

Authors

Hossein Maghsoudi^#^{1

2}, Motahareh Rasoulzadeh³, Maryam Abbastabar^#⁴, Ahmad Fazilat⁵, Farhad Sheikhnia^#^{1

2}, Bita Azizzadeh⁶, Mohamad Valilo^{1

2}, Maryam Majidinia⁷

Affiliations

¹ Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran.
² Department of Clinical Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
³ Department of Toxicology and Pharmacology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁴ Department of Clinical Biochemistry, School of Medicine, Babol University of Medical Sciences, Babol, Iran.
⁵ Motamed Cancer Institute, Breast Cancer Research Center, ACECR, Tehran, Iran.
⁶ Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
⁷ Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran. majidinia.m@umsu.ac.ir.

^# Contributed equally.

Abstract

Colorectal cancer (CRC) ranks as the third most prevalent malignancy and the second leading cause of cancer-related mortality globally. Despite substantial advancements in CRC therapies over recent decades, drug resistance continues to pose a significant challenge in effective treatment. This comprehensive review investigates the role of long non-coding RNAs (lncRNAs) in the emergence of drug resistance in CRC. Specifically, we analyze the functions of lncRNAs, including HOTAIR and MALAT1, in key processes such as apoptosis, DNA damage response and repair, cancer stem cell regulation, and drug metabolism. By examining the structural and biogenetic characteristics of lncRNAs, this review elucidates their specific contributions to drug resistance. We provide novel insights into the therapeutic potential of targeting lncRNAs to mitigate drug resistance in CRC, thereby offering new perspectives on treatment strategies. Ultimately, this review highlights the clinical implications of lncRNA research, emphasizing their potential as targets for innovative therapeutic interventions in colorectal cancer.

Graphical abstract:

Supplementary Information: The online version contains supplementary material available at 10.1186/s12935-025-03951-3.

Keywords: Colorectal cancer; Drug resistance; LncRNAs.

Publication types

Review