RAB3D, upregulated by aryl hydrocarbon receptor (AhR), promotes the progression of prostate cancer by activating the PI3K/AKT signaling pathway.

Many patients with prostate cancer (PCa) cannot be diagnosed until an advanced stage, which make PCa become a large threat to human health. It is an urgent need to explore novel biomarkers for accurate diagnosis and targets for the effective treatment of PCa. This study aimed to investigate the effects of RAB3D (which belongs to the secretory Rab GTPases) on the progression of PCa. The results showed that RAB3D was highly expressed in PCa tissues compared to normal tissues according to the gene expression omnibus dataset. Consistent with the bioinformatics results, RAB3D exhibited a higher expression in PCa cells. Overexpression of RAB3D promoted the proliferation, migration, and invasion of PCa cells, whereas the knockdown of RAB3D led to the opposite results. The procancer effects of RAB3D were further confirmed by the in vivo growth of xenograft model. Subsequently, RAB3D upregulated the PI3K/AKT signaling pathway both in vivo and in vitro. LY294002 (a PI3K inhibitor) rescued the RAB3D upregulation-induced promotion of malignant phenotypes of PCa cells. Furthermore, the transcription activity of RAB3D was found to be enhanced by aryl hydrocarbon receptor (AhR; a transcription factor). The AhR silencing-induced inhibition of the proliferation and migration of PCa cells was reversed by the overexpression of RAB3D. Taken together, RAB3D, upregulated by AhR, promotes the PCa progression by activating the PI3K/AKT signaling pathway.

A rab3 homolog in sea urchin functions in cell division.

Rabs are monomeric GTP binding proteins belonging to the ras superfamily that function throughout the secretory pathway. Members of the rab3 family function in the final steps of the secretory pathway, vesicle fusion with the plasma membrane. In contrast to mammalian systems with several rab3 isoforms (rab3A-D), a single family member homologue of rab3 is present in the rapidly dividing cleavage stage sea urchin embryo that localizes to numerous vesicles enriched at the cell cortex. We hypothesized that whereas the contents of these rab3-positive vesicles may contribute to the embryonic extracellular matrix, the membrane and its constituent proteins may be important for other aspects of cell division. We tested the function of rab3 in cell division by the microinjection of either antibodies or competing effector domain peptides to interfere with its function. We found that perturbing rab3 function results in cessation of cell division, whereas cells injected with either heat-inactivated antibodies or control scrambled peptides develop as normal. Moreover, neither endocytosis nor general membrane topology are affected by rab3 perturbation. Thus, we conclude that rab3-associated vesicles and/or their contents are critical for cell division.