Regulation Mechanism of p-Akt and lncRNA H19 in Colorectal Cancer

Colorectal cancer (CRC) has been a widespread kind of malignant neoplasm worldwide. It has been one of the major contributing reasons for cancer-related deaths globally, with high incidence and mortality; colorectal liver metastases (CRLM) are the main causes of death in CRC patients, and signaling pathway dysregulation-driven abnormal cell proliferation is the core driver of CRC progression. Clarifying the regulatory mechanisms of key molecules in proliferative pathways is critical for developing therapeutic strategies. This study focuses on investigating the abnormal activation of phosphorylated Akt (p-Akt) in the PI3K/Akt pathway during CRC proliferation and the regulatory function of long non-coding RNA (lncRNA) H19. These results show that p-Akt activation in CRC is driven by multiple mechanisms, including overactivation of upstream oncogenic pathways (e.g., HGF/c-Met), abnormal expression of phosphatases (e.g., PRL-3), inactivation of negative regulators (e.g., PTEN), and tumor microenvironment factors (e.g., exosomes). LncRNA H19 is obviously overexpressed in CRC tissues, promoting cell proliferation via ceRNA-mediated mechanisms (e.g., adsorbing miR-200a to upregulate ß -catenin). Notably, H19 regulates p-Akt activation through ceRNA mechanisms to target PI3K/Akt pathway mRNA and protein interactions (e.g., binding to hnRNPA2B1), forming a regulatory network that drives CRC progression. This paper systematically integrates the regulatory relationship between H19 and p-Akt, providing a comprehensive theoretical basis for developing combination-targeted therapies (e.g., H19 siRNA combined with PI3K inhibitors) for CRC.