Long Non-Coding RNA and microRNA Interplay in Colorectal Cancer and Their Effect on the Tumor Microenvironment

Abstract

As the current staging and grading systems are not sufficient to stratify patients for therapy and predict the outcome of the disease, there is an urgent need to understand cancer in its complexity. The mutual relationship between tumour and immune or stromal cells leads to rapid evolution and subsequent genetic and epigenetic changes. Immunoscore has been introduced as a diagnostic tool for colorectal cancer (CRC) only recently, emphasising the role of the specific tumor microenvironment in patient’s prognosis and overall outcome. Despite the fact that non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), cannot be translated into proteins, they significantly affect cell’s transcriptome and translatome. miRNA binding to mRNA efficiently blocks its translation and leads to mRNA destruction. On the other hand, miRNAs can be bound by lncRNAs or circular RNAs (circRNAs), which prevents them from interfering with translation. In this way, ncRNAs create a multi-step network that regulates the cell’s translatome. ncRNAs are also shed by the cell as exogenous RNAs and they are also found in exosomes, suggesting their role in intercellular communication. Hence, these mechanisms affect the tumor microenvironment as much as protein signal molecules. In this review, we provide an insight into the current knowledge of the microenvironment, lncRNAs’, and miRNAs’ interplay. Understanding mechanisms that underlie the evolution of a tissue as complex as a tumour is crucial for the future success in therapy.

Mapping Non-Coding RNAs in Space and Time: Another Weapon to Dissect Intra-Tumor Heterogeneity in Cancer Progression

“…Distinct lncRNA/miRNA/protein regulatory axes have been described in many tumor subtypes, including colorectal cancer (CRC) [7]. As well, reported by Marie Rajtmaierova and colleagues in a recent issue of Cancers [8], these molecular switches can regulate multiple aspects of tumor biology, such as the tumor microenvironment/TME composition or the resistance to chemotherapy. In this regard, it has been shown that lncRNA SCARNA2, found to be upregulated in CRC tissues, can directly activate the miR-342-3p-EGFR/BCL2 axis for escaping 5-fluorouracil cytotoxicity [9].…”

Editorial: The functional role of non-coding RNAs in tumor microenvironment and metastasis of genitourinary tumor and its potential application as tumor molecular biomarkers

“…Changes in the components of TME have a major impact on genitourinary tumor metastasis and lead to poor clinical outcomes. More and more non-coding RNAs (ncRNAs) including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are implicated in TME-mediated carcinogenesis, angiogenesis, invasion, metastasis and chemoresistance ( Liu et al, 2021 ; Jiang et al, 2022 ; Rajtmajerová et al, 2022 ; Xu et al, 2022 ). Clarifying the regulatory link between ncRNAs and TME might aid in the development of innovative therapeutic options for genitourinary malignancies, which would be extremely advantageous in improving the prognosis of patients.…”