Identification of UAP1L1 as tumor promotor in gastric cancer through regulation of CDK6

Abstract

Gastric cancer (GC) is one of the most commonly diagnosed malignancies in digestive tract and its underlying molecular mechanism is still not clear, so we aimed to reveal the relationship between GC and UDP-GlcNAc pyrophosphorylase-1 like 1 (UAP1L1). The detection of UAP1L1 expression in GC tumor and normal tissues was accomplished by immunohistochemistry and demonstrated the upregulation of UAP1L1 in GC, which was statistically associated with tumor grade. GC cell models constructed via transfection of UAP1L1-silencing/ overexpressing lentiviruses were employed for evaluating the effects of UAP1L1 knockdown/overexpression on GC in vitro and in vivo. The results indicated that UAP1L1 played important role in development of GC through regulating cell proliferation, colony formation, cell apoptosis and cell migration. Subsequently, CDK6 was identified as a potential target in UAP1L1 induced regulation of GC, downregulation of which exhibited similar inhibition effects on GC with UAP1L1. Moreover, it was demonstrated that the promotion of GC by UAP1L1 overexpression could be significantly attenuated or even reversed by simultaneously silencing CDK6. In conclusion, UAP1L1 was reported to be a tumor promotor in the development and progression of GC which may exert its role through regulating CDK6 and may act as a candidate of therapeutic target in treatment.

Cyclin B2 (CCNB2) Stimulates the Proliferation of Triple-Negative Breast Cancer (TNBC) Cells In Vitro and In Vivo

“…The cell cycle is tightly and precisely regulated by a variety of regulators, and its abnormalities might lead to tumorigenesis. During the cell cycle, cyclins could bind to the cyclin-dependent kinases (CDKs) to affect expression and the activity of CDKs, therefore mediating cell cycle [ 5 ]. Cyclin B2 (CCNB2), which belongs to B-type cyclins, is a cell cycle regulator [ 6 ].…”

New Prenylated Indole Homodimeric and Pteridine Alkaloids from the Marine-Derived Fungus Aspergillus austroafricanus Y32-2

“…Asperpteridinate A was obtained as a yellow amorphous powder. The molecular formula C 20 [19]. With the aid of the 1 H, 1 H-COSY, HSQC, and HMBC correlations, the structure of 3 was established as shown (Figures 1 and 2).…”

“…Meanwhile, compared to compound 11 , compounds 12 – 14 displayed no anti-inflammatory activity, indicating that both phenolic and alcohol-hydroxyl groups are necessary for anti-inflammatory activity. In addition, all compounds were tested for cytotoxicity against human liver carcinoma cells HepG2 by MTT method ( Table S1 ) [ 20 ], and compound 6 exhibit cytotoxicity with an IC 50 value of 30 µg/mL ( Figure S1 ). The pro-angiogenic, anti-inflammatory activities in zebrafish and cytotoxicity against HepG2 cells of these compounds were reported here for the first time.…”

Silencing of UAP1L1 inhibits proliferation and induces apoptosis in esophageal squamous cell carcinoma

“…In addition, UAP1L1 is also crucial for maintaining the proliferation of human liver cancer cells 13 . Qi et al 24 , highlighted that UAP1L1 promotes gastric cancer by regulating CDK6. Collectively, the promotive role of UAP1L1 in tumor progression has been increasingly characterized.…”