The significance of exosomal non-coding RNAs (ncRNAs) in the metastasis of colorectal cancer and development of therapy resistance.

Abstract

Colorectal cancer (CRC) represents a common type of carcinoma with significant mortality rates globally. A primary factor contributing to the unfavorable treatment outcomes and reduced survival rates in CRC patients is the occurrence of metastasis. Various intricate molecular mechanisms are implicated in the metastatic process, leading to mortality among individuals with CRC. In the realm of intercellular communication, exosomes, which are a form of extracellular vesicle (EV), play an essential role. These vesicles act as conduits for information exchange between cells and originate from multiple sources. By fostering a microenvironment conducive to CRC progression, exosomes and EVs significantly influence the advancement of the disease. They contain a diverse array of molecules, including messenger RNAs (mRNAs), non-coding RNAs (ncRNAs), proteins, lipids, and transcription factors. Notably, ncRNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are prominently featured within exosomes. These ncRNAs have the capacity to regulate various critical molecules or signaling pathways, particularly those associated with tumor metastasis, thereby playing a crucial role in tumorigenesis. Their presence indicates a substantial potential to affect vital aspects of tumor progression, including proliferation, metastasis, and resistance to treatment. This research aims to categorize exosomal ncRNAs and examine their functions in colorectal cancer. Furthermore, it investigates the clinical applicability of novel biomarkers and therapeutic strategies in CRC. Abbreviations: ncRNAs, non-coding RNAs; CRC, Colorectal cancer; EV, extracellular vesicle; mRNAs, messenger RNAs; miRNAs, microRNAs; lncRNAs, long non-coding RNAs; circRNAs, circular RNAs; HOTTIP, HOXA transcript at the distal tip; NSCLC, non-small cell lung cancer; 5-FU, 5-fluorouracil; OX, Oxaliplatin; PDCD4, programmed cell death factor 4; Tregs, regulatory T cells; EMT, epithelial-mesenchymal transition; PFKFB3, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3; USP2, ubiquitin carboxyl-terminal hydrolase 2; TNM, tumor node metastasis; TAMs, tumor-associated macrophages; RASA1, RAS p21 protein activator 1; PDCD4, programmed cell death 4; ZBTB2, zinc finger and BTB domain containing 2; SOCS1, suppressor of cytokine signaling 1; TUBB3, β-III tubulin; MSCs, mesenchymal stem cells.