The Clinical Significance of MicroRNAs in Colorectal Cancer Signaling Pathways: A Review

Abstract

Colorectal carcinoma (colon and rectum) is currently considered among the most prevalent malignancies of Western societies. The pathogenesis and etiological mechanisms underlying colorectal cancer (CRC) development remain complex and heterogeneous. The homeostasis and function of normal human intestinal cells is highly regulated by microRNAs. Therefore, it is not surprising that mutations and inactivation of these molecules appear to be linked with progression of colorectal tumors. Recent studies have reported significant alterations of microRNA expression in adenomas and CRCs compared with adjacent normal tissues. This observed deviation has been proposed to correlate with the progression and survival of disease as well as with choice of optimal treatment and drug resistance. MicroRNAs can adopt either oncogenic or tumor-suppressive roles during regulation of pathways that drive carcinogenesis. Typically, oncogenic microRNAs termed oncomirs, target and silence endogenous tumor-suppressor genes. On the other hand, tumor-suppressive microRNAs are critical in downregulating genes associated with cell growth and malignant capabilities. By extensively evaluating robust studies, we have emphasized and distinguished a discrete set of microRNAs that can modulate tumor progression by silencing specific driver genes crucial in signaling pathways including Wnt/b-catenin, epidermal growth factor receptor, P53, mismatch repair DNA repair, and transforming-growth factor beta.

Unraveling the Multifaceted Role of the miR-17-92 Cluster in Colorectal Cancer: From Mechanisms to Biomarker Potential

“…For instance, the miR-17-92 cluster directly regulates the 3′UTR region of the PTEN gene, resulting in aberrant cell proliferation and atypical angiogenesis [ 42 ]. Furthermore, miR-21, miR-19, and miR-96, prominent oncogenes, have also been implicated in CRC carcinogenesis through their role in stimulating the AKT/PI3K pathway [ 43 ].…”

Insights Into Colorectal Carcinoma: A Comprehensive Review of MicroRNA Expression Patterns

“…The dysregulated expression of miRNAs detected in CRC significantly influences cell survival, apoptosis, epithelial-mesenchymal transition (EMT), and metastasis [14]. As inflammatory mediators, tumor oncogenes, or suppressors, these small noncoding RNAs modulate vital pathways such as Wnt/β-catenin and TGF-β signaling, profoundly impacting CRC tumorigenesis [14,15]. Inflammation and EMT are intricately linked processes in colorectal carcinogenesis, and miRNAs play a pivotal role in their regulation.…”

“…The aberrant activation of the Wnt/β-catenin signaling pathway significantly drives colorectal tumorigenesis. Specific miRNAs, such as miR-135, directly target genes within this pathway, including APC, resulting in heightened Wnt signaling associated with advanced tumor grade and poor prognosis in CRC patients [15]. The therapeutic implications of miRNAs in CRC are profound, as they have emerged as potential targets for intervention.…”

Implications in Cancer of Nuclear Micro RNAs, Long Non-Coding RNAs, and Circular RNAs Bound by PRC2 and FUS

“…Currently, the miRBase database ( ; accessed in 1 December 2023) lists over 2588 distinct miRNAs that are involved in nearly every cellular process, highlighting the vast and complex nature of this field of study [ 7 , 8 ]. Moreover, alterations in miRNA expression have been implicated in a myriad of diseases, emphasizing their importance in maintaining cellular homeostasis [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ].…”