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Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Chinese and other Southeast Asians. We aimed to explore the precise mechanism for NESG1 in NPC for understanding the pathogenesis of NPC. Transwell, Boyden assays, and wounding healing were respectively performed for cell metastasis. The microRNA (miRNA) microarray and luciferase reporter assays were designed to clarify NESG1-modulated miRNAs and miR-1254-targeted protein. Western blotting assays examined the pathways regulated by miR-1254, the (Hepatoma-Derived Growth Factor) HDGF/DDX5 complex, and NESG1. The chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), and co-immunoprecipitation (coIP) assays were used to explore the DNA-protein complex and protein-protein complex. NESG1 suppressed NPC migration and invasion via Wnt/β-catenin signaling. Further, miR-1254 was confirmed as a positive downstream modulator of NESG1 reducing metastatic abilities of NPC cells in vivo and in vitro. Transduction of HDGF significantly restored cell migration and invasion ability in miR-1254-overexpressing NPC cells. In clinical samples, miR-1254 expression was negatively correlated with HDGF and positively correlated with NESG1 expression. miR-1254 acts as an independent prognostic factor for NPC, which was induced by NESG1 to suppress NPC metastasis via inactivating Wnt/β-catenin pathway and its downstream EMT signals.

The pathogenesis and cisplatin chemoresistance of ovarian cancer (OC) are still unclear. Vacuolar protein sorting‐associated 33B (VPS33B) has not been reported in OC to date. In this study, immunohistochemistry was used to detect VPS33B protein expression between OC and ovarian tissues. MTT, EdU, colony formation, cell cycle, in vivo tumorigenesis, western blot, ChIP, EMSA, co‐immunoprecipitation (CoIP), qRT‐PCR, and microconfocal microscopy were used to explore the function and molecular mechanisms of VPS33B in OC cells. The results of the present study demonstrated that VPS33B protein expression was obviously reduced in OC compared with that in ovarian tissues. Overexpressed VPS33B suppressed cell cycle transition, cell growth, and chemoresistance to cisplatin in vitro and in vivo. Analysis of the mechanism indicated that overexpressed VPS33B regulated the epidermal growth factor receptor (EGFR)/PI3K/AKT/c‐Myc/p53/miR‐133a‐3p feedback loop and reduced the expression of the cell cycle factor CDK4. Nasopharyngeal epithelium‐specific protein 1 (NESG1) as a tumor suppressor not only interacted with VPS33B, but was also induced by VPS33B by the attenuation of PI3K/AKT/c‐Jun‐mediated transcription inhibition. Overexpressed NESG1 further suppressed cell growth by mediating VPS33B‐modulated signals in VPS33B‐overexpressing OC cells. Finally, NESG1 induced VPS33B expression by reducing the inhibition of PI3K/AKT/c‐Jun‐mediated transcription. Our study is the first to demonstrate that VPS33B serves as a tumor suppressor, and VPS33B can interact with NESG1 to suppress cell growth and promote cisplatin sensitivity by regulating the EGFR/PI3K/AKT/c‐Myc/p53/miR‐133a‐3p feedback loop in OC cells. [ABSTRACT FROM AUTHOR]

The biological role of vacuolar protein sorting 33B (VPS33B) has not been examined in colorectal cancer (CRC). We report that VPS33B was downregulated in dextran sulfate sodium/azoxymethane (DSS/AOM) ‐induced CRC mice models and nicotine‐treated CRC cells via the PI3K/AKT/c‐Jun pathway. Reduced VPS33B is an unfavorable factor promoting poor prognosis in human CRC patients. VPS33B overexpression suppressed CRC proliferation, intrahepatic metastasis and chemoresistance of cisplatin (DDP) in vivo and in vitro through modulating the epidermal growth factor receptor (EGFR)/RAS/ERK/c‐Myc/p53/miR‐133a‐3p feedback loop and the downstream cell cycle or EMT‐related factors. Furthermore, NESG1 as a newly identified tumor suppressor interacted with VPS33B via colocalization in the cytoplasm, and it was stimulated by VPS33B through the downregulation of RAS/ERK/c‐Jun‐mediated transcription. NESG1 also activated VPS33B expression via the RAS/ERK/c‐Jun pathway. Suppression of NESG1 increased cell growth, migration and invasion via the reversion of the VPS33B‐modulating signal in VPS33B‐overexpressed cells. Taken together, VPS33B as a tumor suppressor is easily dysregulated by chemical carcinogens and it interacts with NESG1 to modulate the EGFR/RAS/ERK/c‐Myc/p53/miR‐133a‐3p feedback loop and thus suppress the malignant phenotype of CRC. What's new? Vacuolar protein sorting 33B (VPS33B) has been suggested to serve as an important tumor suppressor in hepatocarcinogenesis. Here, the authors show that VPS33B is downregulated by chemical carcinogens and poorly expressed in colorectal cancer (CRC) tissues. CRC patients with higher expression of VPS33B have a longer survival time. Furthermore, they demonstrate that VPS33B can interact with NESG1 to suppress cell proliferation, invasion, migration, and intrahepatic metastasis and increase sensitivity to cisplatin via regulating the EGFR/RAS/ERK/c‐Myc/p53/miR‐133a‐3p feedback loop. The data provide novel insight into the significance of VPS33B in CRC and may pave the way for a new treatment strategy. [ABSTRACT FROM AUTHOR]

The article presents research on the effects of human NESG1 (CCD19) gene in nasopharyngeal carcinoma (NPC). The CCD19 gene used in the study was isolated from a human nasopharynx tissue. TheNESG1 transcripts and protein was downregulated or absent in NPC tissues and cell lines in comparison to that in the normal nasopharynx tissues. It concludes that NESG1 may act as a tumor suppressor by inhibiting cell proliferation, invasion, and migration of NPC cells.