Single-cell transcriptomics exposes an uncharacterized lncRNA governing colorectal cancer metastasis

Abstract

Colorectal cancer (CRC) exhibits significant molecular heterogeneity, with long non-coding RNAs (lncRNAs) playing crucial regulatory roles. This study identifies LncRNA01996 as a key oncogenic driver upregulated in CRC tumors compared to adjacent normal tissues, with expression levels correlating directly with advancing cancer stage (Stage I to IV). Mechanistically, LncRNA01996 stabilizes β-catenin, hyperactivating the Wnt signaling pathway while simultaneously suppressing E-CADHERIN expression a critical factor in maintaining cellular adhesion. This dual action promotes cancer cell invasion and metastasis. Additionally, LncRNA01996 transcriptionally activates MYC, amplifying its oncogenic effects.

Clinically, high LncRNA01996 expression is linked to aggressive tumor features, elevated serum markers (CEA, CA19–9), and shorter overall survival in patients. These findings were consistent across patient tissues, cell lines (SW480, SKM), and single-cell RNA sequencing data, confirming its role in diverse CRC microenvironments.

In summary, LncRNA01996 drives CRC progression by dysregulating Wnt/β-catenin signaling, disrupting cell adhesion, and amplifying MYC-driven malignancy. Its strong association with advanced disease and poor outcomes positions LncRNA01996 as a promising prognostic biomarker and a compelling therapeutic target for intercepting CRC metastasis.