Abstract
BACKGROUND: PDZ domain-containing protein 8 (PDZD8) has been implicated in the progression of colorectal cancer. However, its regulatory mechanisms and functional impact remain to be fully elucidated. We assessed PDZD8 expression in colorectal cancer cell lines and normal colorectal mucosa using Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). METHODS: The role of PDZD8 in colorectal cancer was further investigated through the generation of PDZD8-depleted HCT 116 and RKO cell models via short hairpin RNA (shRNA) interference. The influence of PDZD8 knockdown on cellular phenotypes was examined through proliferation, migration, apoptosis, and cell cycle assays. Additionally, the regulatory effect of miR-1283 on PDZD8 was explored both in vitro and in vivo. RESULTS: PDZD8 messenger RNA (mRNA) expression was significantly upregulated in colorectal cancer cell lines compared to normal mucosa, with the highest expression in RKO and HCT 116 cells. PDZD8 knockdown impeded cell proliferation and migration while promoting apoptosis and cell cycle arrest in vitro. Bioinformatics analysis and dual-luciferase assays confirmed miR-1283 as a negative regulator of PDZD8. In vitro and in vivo, PDZD8 overexpression modulated cell viability and migration, increased tumor volume and weight in nude mice, and miR-1283 overexpression counteracted the pro-oncogenic effects of PDZD8. CONCLUSIONS: Our findings revealed that PDZD8 was a critical promoter of malignant phenotypes in colorectal cancer, and its expression was negatively regulated by miR-1283. Targeting the PDZD8/miR-1283 axis may offer a therapeutic strategy for colorectal cancer.