<p>Overexpression of Rab40b Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis via PI3K/AKT Signaling Pathway</p>

Abstract

Background: Rab40b is an evolutionarily conserved Rab GTPase that plays an important role in intracellular trafficking and is closely related to cancer progression. However, the role and potential molecular mechanism of Rab40b in hepatocellular carcinoma (HCC) have not yet been elucidated. Materials and Methods: The expression of Rab40b in HCC tissues and peritumour tissues was tested by qRT-PCR, Western blotting and histological analysis. A Kaplan-Meier survival curve was generated based on the expression of Rab40b in the HCC samples. Cell proliferation assays, wound healing assays, and transwell assays are used to examine the effect of Rab40b on HCC cell growth in vitro. The effect of Rab40b on cell cycle was examined by flow cytometry. A xenograft implantation model was used to assess the effect of Rab40b on the development of HCC cells in vivo. Results: Rab40b protein expression is upregulated in HCC tissues, and this upregulation is associated with high pathological stage and poor prognosis in HCC patients. Rab40b overexpression promotes the proliferation and metastasis of HCC cells by upregulating cyclin D1, cyclin E1 and matrix metalloproteinase 2 (MMP2) through the PI3K/AKT signalling pathway. Conversely, Rab40b inhibitors can significantly inhibit the proliferation and metastasis of HCC cell lines and induce G0/G1 cell cycle arrest and apoptosis. Studies of a nude mouse xenograft model demonstrated that Rab40b knockdown can significantly inhibit the proliferation and progression of HCC tumours in vivo. Conclusion: Overall, this study demonstrates that Rab40b is an important oncoprotein that promotes HCC progression by regulating the expression of cyclin D1, cyclin E1, p21 and MMP2 through the PI3K/AKT signalling pathway.

Effects of plasma-derived exosomes from the normal and thin Bactrian camels on hepatocellular carcinoma and their differences at transcriptome and proteomics levels

“…In addition, angiogenin is a stress-induced secreted ribonuclease with nuclear and cellular solute activities, and involved in normal development and disease ( 52 ). Ras-related protein Rab-11B is a key regulator of intracellular transport and endocytic pathway ( 53 ), and Rab proteins play important roles in HCC progression ( 54 ). Kinase suppressor of Ras 1 has been reported to attenuate neurostatin secretion and extracellular signal-regulated kinase 1 and 2 signaling in human endocrine cells, thereby participating in obesity-related metabolic disorders and Ras-driven cancer ( 55 ).…”

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

“…When the pathway is activated, AKT can promote a series of biological effects closely related to cell physiological activities by activating downstream effector molecules (Vivanco & Sawyers, 2002). Shi et al (2020) have suggested that RAB40b aggravates the proliferation and metastasis of cancer cells by upregulating cyclin D1, cyclin E1, and MMP2 through the PI3K/AKT signaling pathway. RAB3D is reported to involve in the progression of various cancers by regulating the PI3K/AKT signaling (Zhang et al, 2017).…”

Effects of plasma-derived exosomes from the normal and thin camels on hepatocellular carcinoma and their differences at transcriptome and proteomics levels

“…In addition, angiogenin is a stress-induced secreted ribonuclease with nuclear and cellular solute activities, and involved in normal development and disease 33 . Ras-related protein Rab-11B is a key regulator of intracellular transport and endocytic pathway 34 , and Rab proteins play important roles in HCC progression 35 . Kinase suppressor of Ras 1 has been reported to attenuate neurostatin secretion and extracellular signal-regulated kinase 1 and 2 signaling in human endocrine cells, thereby participating in obesity-related metabolic disorders and Ras-driven cancer 36 .…”