LAUSR

Simple Summary Nearly two decades would be required for a cancer lesion to develop from normal colon mucosa, but most colorectal cancer (CRC) patients are at an advanced stage at presentation. Chemotherapy, targeted therapy, and radiotherapy can improve the prognosis of patients with advanced CRC, but sometimes the therapy resistance occurs, and the 5-year survival rate for patients with locally advanced CRC and with metastatic CRC (mCRC) remain poor. MicroRNAs (miRs) can regulate cancer pathways by inhibiting their target mRNA translation and triggering their degradation. MiRs can serve as predictive biomarkers for the detection of CRC or mCRC or the resistance of chemotherapy or chemoradiotherapy, and miRNA-based therapeutics may finally reach the clinical stages. Abstract Colorectal cancer (CRC) is one of the most common malignancies and is associated with high mortality rates worldwide. The underlying mechanism of tumorigenesis in CRC is complex, involving genetic, lifestyle-related, and environmental factors. Although radical resection with adjuvant FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) chemotherapy and neoadjuvant chemoradiotherapy have remained mainstays of treatment for patients with stage III CRC and locally advanced rectal cancer, respectively, the oncological outcomes of these treatments are often unsatisfactory. To improve patients’ chances of survival, researchers are actively searching for new biomarkers to facilitate the development of more effective treatment strategies for CRC and metastatic CRC (mCRC). MicroRNAs (miRs), small, single-stranded, noncoding RNAs, can post-transcriptionally regulate mRNA translation and trigger mRNA degradation. Recent studies have documented aberrant miR levels in patients with CRC or mCRC, and some miRs are reportedly associated with chemoresistance or radioresistance in CRC. Herein, we present a narrative review of the literature on the roles of oncogenic miRs (oncomiRs) and tumor suppressor miRs (anti-oncomiRs), some of which can be used to predict the responses of patients with CRC to chemotherapy or chemoradiotherapy. Moreover, miRs may serve as potential therapeutic targets because their functions can be manipulated using synthetic antagonists and miR mimics.