Regulatory mechanism of LINC00657/MiR-26b in the TNF-α/NF-κB pathway for the progression of colorectal cancer

Abstract

This study investigates the effect of long-chain non-coding LINC00657 on cell proliferation and apoptosis in colorectal cancer and its molecular mechanism based on magnetic nanocarriers for gene delivery. Tumor tissues were collected from patients with colorectal cancer (CRC) to examine the expression of LINC00657. Magnetic nano microspheres were prepared and CRC cells were transfected with short hairpin RNA (shRNA) targeting LINC00657 to establish a stably transfected cell line. The binding relationship between LINC00657 and MicroRNA-26b (MiR-26b) was also verified using a dual-luciferase gene reporter assay. The expression of LINC00657 and MiR-26b were determined by qRT-PCR and Western blot. Cell proliferation, migration, and apoptosis were assessed. Our findings reveal that LINC00657 is highly expressed in CRC tissues and cells, significantly promoting hepatoma carcinoma cell proliferation and migration. Furthermore, we demonstrate that MiR-26b can target and bind to LINC00657, while its expression decreases in CRC cells. Knockdown of LINC00657 resulted in significant downregulation of both MiR-26b expression levels and tumor necrosis factor-α (TNF-α)/nuclear factor-kappa B (NF-κB) pathway activity. However, co-transfection of a MiR-26b inhibitor into sh-LINC00657-transfected cells attenuated the effects on malignant phenotypes while activating TNF-α/NF-kB pathway activity. Conversely, transfection of an NF-kB activator exerted similar effects as the MiR-26b inhibitor by enhancing malignant proliferation ability in CRC cells. Overall, the upregulation of LINC00657 potentially modulates the proliferation and apoptosis of colorectal cancer cells through its interaction with MiR-26b, leading to the activation of the TNF-α/NF-κB signaling pathway.