Differential Expression of MicroRNAs in the Colorectal Serrated Neoplasia Pathway and Adenoma–Carcinoma Sequence

<b>Background and Aim:</b> Colorectal carcinogenesis involves two distinct pathways, the serrated neoplasia pathway and adenoma (AD)-carcinoma sequence, whose precursors are sessile serrated lesion (SSL) and traditional AD, respectively. MicroRNAs (miRNAs) regulate gene expression and play a crucial role in colorectal tumorigenesis. This study investigated miRNA expression in the precursors and early invasive carcinomas of the two pathways. <b>Methods:</b> Using real-time reverse transcription polymerase chain reaction, we quantified the expression of miR-20a, miR-21, miR-93, and miR-181b in 127 lesions, including 25 SSLs, 19 SSLs with high-grade dysplasia (SSL-HD), 13 SSLs with submucosal invasive carcinoma (SSL-SC), 19 ADs, 26 ADs with HD (AD-HD), and 25 ADs with SC (AD-SC). <b>Results:</b> In the SSL series, miR-93 (SSL vs. SSL-SC, <i>p</i> = 0.038) and miR-181b (SSL vs. SSL-HD/SSL-SC, <i>p</i> = 0.013/<i>p</i> < 0.001, respectively) levels decreased with tumor progression. In the AD lineage, the expression of miR-20a (AD vs. AD-SC and AD-HD vs. AD-SC, <i>p</i> < 0.001), miR-21 (AD vs. AD-HD/AD-SC and AD-HD vs. AD-SC, <i>p</i> < 0.001), and miR-181b (AD-HD vs. AD-SC, <i>p</i> = 0.020) increased during carcinogenesis. Compared with normal mucosa (baseline), miR-93 expression showed a stepwise increase with tumor progression in the AD lineage, whereas the values did not change during SSL carcinogenesis. In the AD lineage, miR-20a expression increased in early invasive carcinoma but decreased in this phase of the SSL series. Overall, miR-20a, miR-93, and miR-181b levels were significantly lower in SSL-SC than in AD-SC (all <i>p</i> < 0.001). <b>Conclusions:</b> These findings indicate that the SSL and AD pathways exhibit distinct miRNA expression dynamics during colorectal tumorigenesis, with the AD lineage showing a progressive increase in oncogenic miRNAs and the SSL series exhibiting selective downregulation or plateauing, particularly in invasive lesions. The differential expression of miR-20a, miR-21, miR-93, and miR-181b was presumed to be related to (epi)genetic alterations among serrated neoplasia and AD-carcinoma routes.