Dataset Information

STK35 Is Ubiquitinated by NEDD4L and Promotes Glycolysis and Inhibits Apoptosis Through Regulating the AKT Signaling Pathway, Influencing Chemoresistance of Colorectal Cancer.

ABSTRACT: The development of colorectal cancer (CRC) is often sporadic, but its etiology is multifactorial. Chemoresistance of CRC leads to tumor recurrence and poor prognosis in patients. The phosphorylation of protein kinase B (AKT) can activate metabolic reprogramming toward cellular glycolysis. Serine/threonine kinase 35 (STK35) regulates the cell cycle and is frequently associated with cancer progression, whereas little is known about its specific roles in CRC. In the current study, bioinformatics analyses were performed to investigate the relationship between STK35 and CRC prognosis. STK35 knockdown and overexpressing CRC cells were established to examine its functions in CRC. Fluorouracil (5-FU) was utilized to evaluate the effect of STK35 on CRC chemoresistance. Moreover, co-immunoprecipitation was performed to explore the ubiquitination of STK35. STK35 was highly expressed in CRC, and its protein expression was negatively correlated with the survival of CRC patients. Furthermore, STK35 overexpression could promote glycolysis, suppress apoptosis, upregulate p-AKT, and counteract the antitumor functions of 5-FU and neural precursor cell expressed developmentally downregulated gene 4-like (NEDD4L) in CRC cells. NEDD4L was associated with and could ubiquitinate STK35. STK35 could be a prognostic biomarker for CRC prognosis and has promotive effects on CRC cellular activities, partially through the AKT pathway. Moreover, STK35 also interferes with the chemosensitivity of CRC.

SUBMITTER: Yang H

PROVIDER: S-EPMC7578231 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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STK35 Is Ubiquitinated by NEDD4L and Promotes Glycolysis and Inhibits Apoptosis Through Regulating the AKT Signaling Pathway, Influencing Chemoresistance of Colorectal Cancer.

Yang Haojun H Zhu Jie J Wang Guangyao G Liu Hanyang H Zhou Yan Y Qian Jun J

Frontiers in cell and developmental biology 20201008

The development of colorectal cancer (CRC) is often sporadic, but its etiology is multifactorial. Chemoresistance of CRC leads to tumor recurrence and poor prognosis in patients. The phosphorylation of protein kinase B (AKT) can activate metabolic reprogramming toward cellular glycolysis. Serine/threonine kinase 35 (STK35) regulates the cell cycle and is frequently associated with cancer progression, whereas little is known about its specific roles in CRC. In the current study, bioinformatics an ...[more]

PMID: 33117809

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Project description:BackgroundColorectal cancer (CRC) poses a heavy threat to human health owing to its high incidence and mortality. Circular RNAs (circRNAs) were investigated to participate in the progression of CRC, whereas there was no revenant data on the CRC process regulated by hsa_circ_0000231. This study aimed to explore the effects of hsa_circ_0000231 on CRC progression and underneath regulatory mechanism.MethodsThe expression levels of hsa_circ_0000231, miR-502-5p, and Myosin VI (MYO6) mRNA were detected by quantitative real time polymerase chain reaction (qRT-PCR). Western blot was employed to determine the protein expression levels of MYO6 and proliferating cell nuclear antigen (PCNA). The effects of hsa_circ_0000231 on cell proliferation, apoptosis, migration, and invasive in CRC were determined by cell counting kit-8 proliferation (CCK-8) and colony formation assays, flow cytometry analysis, wound-healing assay, and transwell invasion assay, respectively. Glucose uptake and lactate production were severally illustrated by glucose assay kit and lactate assay kit. The relationship between miR-502-5p and hsa_circ_0000231 or MYO6 was predicted by circular RNA interactome or targetScan online databases, and identified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. In vivo tumor formation assay was carried out to determine the effects of hsa_circ_0000231 knockdown on tumor growth in vivo.ResultsHsa_circ_0000231 expression was dramatically upregulated while miR-502-5p was obviously downregulated in CRC tissues and cells compared with control groups. Hsa_circ_0000231 knockdown repressed the expression levels of MYO6 and PCNA protein. Functionally, hsa_circ_0000231 knockdown repressed cell glycolysis, proliferation, migration and invasion, and induced cell apoptosis, whereas these effects were decreased by miR-502-5p inhibitor. Mechanistically, hsa_circ_0000231 acted as a sponge of miR-502-5p and miR-502-5p bound to MYO6. Furthermore, hsa_circ_0000231 knockdown decreased tumor volume and weight of CRC in vivo.ConclusionHsa_circ_0000231 knockdown inhibited CRC progression and glycolysis by downregulating MYO6 expression through sponging miR-502-5p, which might provide a theoretical basis in further studying circ_0000231-directed therapy in CRC.

Dataset Information

STK35 Is Ubiquitinated by NEDD4L and Promotes Glycolysis and Inhibits Apoptosis Through Regulating the AKT Signaling Pathway, Influencing Chemoresistance of Colorectal Cancer.

Publications

STK35 Is Ubiquitinated by NEDD4L and Promotes Glycolysis and Inhibits Apoptosis Through Regulating the AKT Signaling Pathway, Influencing Chemoresistance of Colorectal Cancer.

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