Has-mir-۴۲۱ in Colorectal Cancer: Expanding Diagnostic and Therapeutic Frontiers

Introduction: Colorectal cancer (CRC) represents a highly malignant neoplasm within the digestive tract andstands as a leading cause of cancer-related mortality worldwide. MicroRNAs (miRNAs), small non-codingRNAs typically approximately ۲۲ nucleotides in length, and exert regulatory control over gene expression. Amultitude of miRNAs have been associated with carcinogenesis, tumor proliferation, and metastasis in CRC,suggesting their promise as both diagnostic biomarkers and therapeutic targets in the disease. Among these,miR-۴۲۱ has demonstrated distinct potential in the diagnosis and treatment of various cancers. Nonetheless, acomprehensive understanding of miR-۴۲۱ in the context of CRC is currently lacking, prompting the initiationof a systematic review with the objective of exploring its viability as a diagnostic biomarker and therapeutictarget in CRC.Methods: A systematic search was conducted for articles containing the keywords "colorectal neoplasm,” “hsamiR-۴۲۱,” and “miRNA-۴۲۱” across the period from ۲۰۱۳ to ۲۰۲۳ in databases such as PubMed, Scopus, andWeb of Science. Following this, rigorous application of predetermined exclusion and inclusion criteria resultedin the identification of six articles deemed suitable for inclusion in the studyConclusion: The expression of miR-۴۲۱ was markedly decreased in CRC tissues and cells when compared toadjacent normal tissues and normal human intestinal epithelial cells. MiR-۴۲۱ demonstrated the ability torestrain the proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) of CRC cellsthrough direct regulation of the target gene MTA۱, effectively suppressing the carcinogenic potential of CRCcells. Additionally, the long non-coding RNA TUG۱ was observed to bind to miR-۴۲۱, leading to increasedexpression of KDM۲A, a target gene of miR-۴۲۱, and subsequent activation of the ERK pathway by increasedKDM۲A expression level. Moreover, SP۱ was found to promote the tumorigenesis of CRC cells in vivo byregulating the TUG۱/miR-۴۲۱/KDM۲A/ERK axis. On the plus side, miR-۴۲۱ was found to be significantlyupregulated in the feces of CRC patients compared to controls. Therefore, the miR-۴۲۱ is expected to be anoninvasive diagnostic biomarker and a promising therapeutic target for CRC.