Wenbo Zhang

Hepatocellular carcinoma (HCC) lacks effective early diagnostic markers and is heavily driven by angiogenesis and hypoxia. Emerging evidence indicates that metabolic enzymes and noncoding RNAs coordinate these processes. Here, we reveal that phosphoserine phosphatase (PSPH), a serine biosynthesis enzyme, is significantly upregulated in HCC, correlating with angiogenic markers and poor prognosis. Clinical data and functional assays demonstrated that miR-101-3p directly targets the PSPH 3′ UTR to suppress its expression, while lncRNA GSEC acts as a competing endogenous RNA to sponge miR-101-3p. In vitro, GSEC knockdown or miR-101-3p overexpression decreased PSPH and HIF1α levels, strongly inhibiting HCC angiogenesis, migration, invasion, and proliferation. Crucially, these anti-tumor effects were reversed by restoring PSPH. In vivo, modulating the GSEC/PSPH axis significantly altered xenograft tumor growth and vascularization. Conclusively, the GSEC/miR-101-3p/PSPH regulatory axis drives HIF1α-dependent angiogenesis and HCC progression, highlighting PSPH as a promising diagnostic biomarker and therapeutic target.

Increasing evidence suggests that RHBDD2 is involved in the development and progression of a variety of tumors, but its role in colorectal adenocarcinoma (COAD) remains unclear. Therefore, the aim of our study was to investigate the exact role of RHBDD2 in COAD. The expression levels of RHBDD2 in COAD were analyzed based on The Cancer Genome Atlas (TCGA) database. Survival analysis of RHBDD2 in COAD was analyzed using the TCGA dataset. In addition, the functional role of RHBDD2 was detected by GO, KEGG, and immune infiltration analysis. The results showed that RHBDD2 was significantly upregulated in COAD samples. High RHBDD2 expression in COAD was significantly correlated with T, N, and M stages and pathological stage. Elevated RHBDD2 expression was unfavorable for overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS). Receiver operating characteristic (ROC) analysis showed that RHBDD2 may serve as a potential diagnostic biomarker for COAD patients. In addition, RHBDD2 was significantly correlated with the level of immune cell infiltration. The current study suggests that elevated RHBDD2 expression is closely associated with poor prognosis and immune cell infiltration in COAD, and may serve as a promising independent prognostic biomarker and potential therapeutic target.