miR-27a-3p targets CACNA2D3 to promote colorectal cancer progression via the Ca/ROS/mitochondrial apoptotic pathway.

Targeted therapy, as an effective therapeutic strategy for the treatment of colorectal cancer (CRC), is still limited by its applicability to specific patient populations and drug resistance. Therefore, there is an urgent need to elucidate the molecular mechanisms underlying the development of CRC and identify novel targeted biomarkers. CACNA2D3 encodes the α2δ3 subunit of calcium (Ca) channels, and recent studies have consistently demonstrated its potential as a tumor suppressor. MicroRNAs (miRNAs) act by binding to the 3'-UTR of mRNAs to inhibit the function of target genes. Currently, the underlying mechanisms of CACNA2D3 and its upstream miRNAs in CRC remain elusive. Our study revealed that CACNA2D3, which is expressed at low levels in CRC, inhibits CRC cell proliferation and promotes apoptosis by up-regulating intracellular Ca and ROS levels and activating the mitochondrial apoptotic pathway. miR-27a-3p, whose expression level is significantly upregulated in CRC, is an upstream miRNA of CACNA2D3, and promote the progression of CRC by negatively regulating CACNA2D3.By exploring the mechanism of action of CACNA2D3 in colorectal cancer and identifying potential upstream microRNAs, we aim to provide a new strategy for targeted therapy for CRC.