Hdlbp-flox Mouse

HDLBP, also known as vigilin, is a member of an evolutionarily conserved family of RNA-binding proteins. It contains 14 or 15 RNA-interacting KH domains and is involved in multiple processes such as translation, chromosome segregation, cholesterol transport, and carcinogenesis. It is mainly present at the cytoplasmic face of the endoplasmic reticulum, and also in the cytosol and nucleus [3].

In hepatocellular carcinoma (HCC), HDLBP has been shown to have several roles. Knockdown of HDLBP inhibits HCC cell proliferation, sorafenib resistance, metastasis, and invasion. HDLBP stabilizes lncFAL, which in turn reduces ferroptosis vulnerability by competitively abolishing Trim69-dependent FSP1 polyubiquitination degradation. It also stabilizes RAF1 protein by competing with TRIM71 E3 ligase, leading to HCC progression and sorafenib resistance. Additionally, HDLBP promotes HCC metastasis through BRAF-dependent epithelial-mesenchymal transition by inhibiting BRAF ubiquitinated degradation [1,2,4].

In small cell lung cancer (SCLC), attenuating HDLBP expression with siRNA inhibits cell proliferation, metastasis in vitro, and tumor formation in vivo, as HDLBP promotes G1/S cell cycle transition for tumor progression [6]. In lung adenocarcinoma, HDLBP promotes glycolysis and CD8+ T cell exhaustion by stabilizing GJB2 RNA [5].

In conclusion, HDLBP is an important RNA-binding protein involved in multiple biological processes, especially in cancer development. Studies using loss-of-function models, such as siRNA-mediated knockdown in cancer cells, have revealed its significant roles in HCC, SCLC, and lung adenocarcinoma, providing potential targets for cancer treatment.