MALAT1/miR-145 Axis Links Inflammatory, Fibrotic, and Apoptotic Pathways in Colorectal Cancer

Colorectal cancer (CRC) is a complex malignancy where aberrant signaling networks and noncoding RNA regulators drive progression and metastasis. Liver metastasis, in particular, remains a primary cause of mortality. Current therapeutic strategies often fall short in addressing the intricate interplay between inflammatory, fibrotic, and apoptotic pathways that fuel tumor growth. The long noncoding RNA MALAT1 and microRNA miR-145 are recognized as potential diagnostic biomarkers, yet their precise biochemical interaction and molecular correlation with key oncogenic pathways like NF-κβ and TGF-β in CRC have remained underexplored, representing a critical gap in understanding disease pathogenesis.

Researchers collected serum samples from a total of 120 participants, comprising 90 colorectal cancer patients with varying tumor grades and anatomical sites, alongside 30 healthy controls. The study aimed to evaluate the biochemical interaction of the MALAT1/miR-145 axis and its connection to the NF-κβ/TGF-β signaling pathway, as well as crosstalk with VEGF and apoptotic markers. Expression levels of NF-κβ and apoptotic markers were quantified using standardized immunoassays. The relative expression levels of MALAT1, miR-145, TGF-β, and VEGF were precisely assessed using real-time polymerase chain reaction (qPCR).

Integrative analysis of CRC patient samples revealed a significant biochemical signature. MALAT1 overexpression consistently correlated with the downregulation of miR-145. This dysregulation was further linked to a pronounced increase in NF-κβ expression, elevated levels of TGF-β, and heightened VEGF expression. Furthermore, the study observed significant alterations in the expression of apoptotic proteins, suggesting a direct impact on programmed cell death mechanisms. The MALAT1/miR-145 axis appears to serve as a central node, bridging inflammatory and fibrotic signaling pathways with apoptotic protein expression in colorectal carcinogenesis. The discriminative power of MALAT1 and miR-145 in distinguishing CRC patients from healthy controls was assessed using receiver operating characteristic (ROC) analysis, which revealed > excellent discriminative power for both biomarkers, highlighting their potential as diagnostic tools. These findings underscore the intricate regulatory network at play, where MALAT1 and miR-145 orchestrate critical processes influencing tumor progression.