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BACKGROUND Colorectal cancer (CRC), is the third most common cancer type. MicroRNAs and their roles in cancer progression have gained considerable attention in the scientific community. miR-485-3p has been identified to be abnormally expressed in different types of cancer, but its expression level, biological function, and underlying pathways are still unclear in CRC. Targeting Protein for Xenopus kinesin-like protein 2 (TPX2) is a nuclear protein which plays vital roles in cancer progression and mitotic spindle assembly. TPX2 is overexpressed in various malignancies and has been predicted as an indirect target of miR-485-3p. This study aims to investigate the miR-485-3p and TPX2 expression level, their potential correlation, and underlying molecules like P53 and P21 in forty-one pairs of colorectal cancer tissues compared to matched non-cancerous ones. MATERIALS AND METHODS We used forty-one pairs of CRC fresh tissue samples and their adjacent normal ones for RNA extraction. After cDNA synthesis, the expression level of miR-485-3p, TPX2, P53 and P21 were determined by Real-time PCR. RESULTS AND CONCLUSIONS The results revealed that miR-485-3p was significantly downregulated and TPX2 was highly upregulated in CRC tissues. Moreover, miR-485-3p was negatively correlated with TPX2 expression and positively correlated with P21 expression. We present miR-485-3p as a suppressor for colorectal cancer (Tab. 2, Fig. 8, Ref. 44).