Non-Coding RNAs Implicated in the Tumor Microenvironment of Colorectal Cancer: Roles, Mechanisms and Clinical Study

Abstract

Colorectal cancer (CRC) is one of the most common malignant tumors. The morbidity and mortality rates have been increasing all over the world. It is critical to elucidate the mechanism of CRC occurrence and development. However, tumor microenvironment (TME) includes immune cells, fibroblasts, endothelial cells, cytokines, chemokines and other components that affect the progression of CRC and patients’ prognosis. Non-coding RNAs (ncRNAs) including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) without protein-coding ability have been shown to engage in tumor microenvironment-mediated angiogenesis and metastasis. Therefore, clarifying the mechanism of ncRNAs regulating the microenvironment is very important to develop the therapeutic target of CRC and improve the survival time of patients. This review focuses on the role and mechanism of ncRNAs in the CRC microenvironment and puts forward possible clinical treatment strategies.

An Overview of the Immune Modulatory Properties of Long Non-Coding RNAs and Their Potential Use as Therapeutic Targets in Cancer

“…In colorectal cancer, it was reported that the tumor suppressor miR-195-5p promotes TAM polarization by suppressing NOTCH2 expression [85]. Furthermore, exosomal miRNAs (e.g., miR-934, miR-25-3p, miR-130b-3p, miR-425-5p) can induce the activation of the CXCL13/CXCR5 or CXCL12/CXCR4 axis in colorectal cancer cells, which in turn activate TAM polarization and metastasis to liver [86]. On the other hand, lncRNAs such as lnc-EGFR, SNHG1, Flicr, and Flatr can orchestrate the correct function and differentiation of Treg cells [86].…”

“…Furthermore, exosomal miRNAs (e.g., miR-934, miR-25-3p, miR-130b-3p, miR-425-5p) can induce the activation of the CXCL13/CXCR5 or CXCL12/CXCR4 axis in colorectal cancer cells, which in turn activate TAM polarization and metastasis to liver [86]. On the other hand, lncRNAs such as lnc-EGFR, SNHG1, Flicr, and Flatr can orchestrate the correct function and differentiation of Treg cells [86]. Moreover, lnc-EGFR has also been shown to stimulate Treg differentiation, inhibit cytotoxic T lymphocyte activity, and induce hepatocellular carcinoma (HCC) growth [87].…”

Immune Modulatory Long-Non-Coding RNA as a Potential Therapeutic Target in Cancer

“…In colorectal cancer, it was reported that tumor suppressor miR-195-5p promotes TAM polarization by the suppression of NOTCH2 expression (30). Furthermore, the exosomal miRNAs (miR-934, miR-25-3p, miR-130b-3p, miR-425-5p) can induce the activation of the CXCL13/CXCR5 or CXCL12/CXCR4 axis in colorectal cancer cells, which in turn activate TAM polarization and metastasis to liver (31). On the other hand, lncRNAs such as lnc-EGFR, lncRNA SNHG1, Flicr, and Flatr can orchestrate the correct function and differentiation of Tregs (31).…”

“…Furthermore, the exosomal miRNAs (miR-934, miR-25-3p, miR-130b-3p, miR-425-5p) can induce the activation of the CXCL13/CXCR5 or CXCL12/CXCR4 axis in colorectal cancer cells, which in turn activate TAM polarization and metastasis to liver (31). On the other hand, lncRNAs such as lnc-EGFR, lncRNA SNHG1, Flicr, and Flatr can orchestrate the correct function and differentiation of Tregs (31). Moreover, lnc-EGFR has also been shown to stimulate Treg differentiation, inhibit cytotoxic T lymphocyte activity, and induce hepatocellular carcinoma (HCC) growth (32).…”