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- W4235780672 abstract "Abstract Background Glycolysis plays an essential role in the growth and metastasis of solid cancer and has received increasing attention in recent years. However, the complex regulatory mechanisms of tumour glycolysis remain elusive. This study aimed to explore the molecular effect and mechanism of the noncoding RNA miR-103a-3p on glycolysis in colorectal cancer (CRC). Methods We explored the effects of miR-103a-3p on glycolysis and the biological functions of CRC cells in vitro and in vivo . Furthermore, we investigated whether miR-103a-3p regulates HIF1A expression through the Hippo/YAP1 pathway, and evaluated the role of the miR-103a-3p-LATS2/SAV1-YAP1-HIF1A axis in promoting glycolysis and angiogenesis in CRC cells and contributing to invasion and metastasis of CRC cells. Results We found that miR-103a-3p is highly expressed in CRC tissues and cell lines compared with matched controls and the high expression of miR-103a-3p is associated with poor patient prognosis. Under hypoxic conditions, a high level of miR-103a-3p can promote the proliferation, invasion, migration, angiogenesis and glycolysis of CRC cells. Moreover, miR-103a-3p knockdown inhibits the growth, proliferation, and glycolysis of CRC cells and promotes the Hippo-YAP signalling pathway in nude mice in a xenograft model. Here, we demonstrated that miR-103a-3p could directly target LATS2 and SAV1. Subsequently, we verified that TEAD1, a transcriptional coactivator of Yes-associated protein 1 (YAP1), directly binds to the HIF1A promoter region and the YAP1 and TEAD1 proteins could co-regulate the expression of HIF1A, thus promoting tumour glycolysis. Conclusions MiR-103a-3p, which is highly expressed in CRC cells, promotes HIF1A expression by targeting the core molecules LATS2 and SAV1 of the Hippo/YAP1 pathway, contributing to enhanced proliferation, invasion, migration, glycolysis and angiogenesis in CRC. Our study revealed the functional mechanisms of miR-103a-3p/YAP1/HIF1A axis in CRC glycolysis, which would provide potential intervention targets for molecular targeted therapy of CRC." @default.
- W4235780672 created "2022-05-12" @default.
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- W4235780672 date "2020-05-23" @default.
- W4235780672 modified "2023-09-23" @default.
- W4235780672 title "MiR-103a-3p promotes tumour glycolysis in colorectal cancer via Hippo/YAP1/HIF1A axis" @default.
- W4235780672 doi "https://doi.org/10.21203/rs.3.rs-30025/v1" @default.
- W4235780672 hasPublicationYear "2020" @default.
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