4.6 Article

ELOA promotes tumor growth and metastasis by activating RBP1 in gastric cancer

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CANCER MEDICINE
卷 -, 期 -, 页码 -

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WILEY
DOI: 10.1002/cam4.6516

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elongin A; gastric cancer; metastasis; miR-490-3p; RBP1; transcription

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In this study, we found that ELOA is upregulated in gastric cancer and is associated with malignant characteristics and poor prognosis. Functional experiments showed that ELOA promotes gastric cancer proliferation and metastasis. Mechanistic studies revealed that ELOA exerts its oncogenic properties by activating the expression of RBP1.
Background Elongin A (ELOA), our previous work revealed, serves as a novel tumor suppressor in colorectal cancer. However, the function and mechanism of ELOA in other cancer types, including gastric cancer (GC), remain to be elucidated.Methods The expression of ELOA was measured by quantitative reverse transcription-polymerase chain reaction and western blot. The effects of ELOA on GC growth and metastasis were assessed through a series of in-vitro and in-vivo assays. Furthermore, the potential mechanism of ELOA was revealed by RNA sequencing, dual luciferase reporter assay, chromatin immunoprecipitation, and rescue experiments in GC.Results We uncovered increased expression of ELOA in GC tissues compared with paired normal tissues via bioinformatic analyses and our sample detection. Enhanced ELOA expression in GC tissues was obviously correlated with poor tumor differentiation, lymph node metastasis, advanced tumor stage, and a poor prognosis. A series of functional experiments showed that ELOA promoted the proliferation and metastasis of GC. Mechanistically, we revealed that the decreased levels of miR-490-3p caused the upregulation of ELOA in GC. Both RNA-seq and ChIP assays revealed that ELOA transcriptionally activated retinol-binding protein 1 (RBP1) by binding to its promotor. Furthermore, specific knockdown of RBP1 reduced the tumor-promoting ability of ELOA in GC cells.Conclusions In summary, our findings demonstrate that ELOA exerts oncogenic properties by activating RBP1 expression, providing the basis for a promising therapeutic target in GC.

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