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bioRxiv · 10.1101/2023.08.30.555568

Hsa_circ_0005397 could promote hepatocellular carcinoma progression and metastasis through EIF4A3

Yuan, L.·Luo, M.·Liu, R.-Y.·Wang, H.-X.·Ju, L.-L.·Wang, F.·Cao, L.-Y.·Wang, Z.-C.·Chen, L.
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Abstract

PurposeThe purpose was to explore the expression and potential mechanism of hsa_circ_0005397 in hepatocellular carcinoma metabolism. MethodsThe quantitative real-time PCR (qPCR) was used to measure the expression of hsa_circ_0005397 and EIF4A3. The specificity of primers was confirmed by agarose gel electrophoresis. The ROC curve was draw to analysis clinical value. The actinomycin D assay and Nuclear and Cytoplasmic Extraction assay were utilized to evaluate the characteristic of hsa_circ_0005397. The CCK-8 and colony formation assays were performed to detect cell proliferation. The flow cytometry analysis was used to detect the cycle distribution. The transwell assays and Xenograft tumor model were conducted to explore cell metabolism. The RNA-binding proteins of hsa_circ_0005397 in HCC were explored in bioinformatics websites. The relationship between hsa_circ_0005397 and EIF4A3 was verified by RIP assays and rescue experiments. ResultsHsa_circ_0005397 and EIF4A3 were overexpressed in HCC. Through ROC analysis, hsa_circ_0005397 shown a big role in diagnosis and prognosis. Hsa_circ_0005397 was stable and almost distributed in the cytoplasm. The upregulation of hsa_circ_0005397 generally resulted in stronger proliferative ability, clonality, metastatic potency of HCC cells, while downregulation of hsa_circ_0005397 yielded opposite results. Tumor volume and size were notably reduced while downregulation of hsa_circ_0005397, showing significant difference in tumor growth. EIF4A3 was the RNA-binding protein of hsa_circ_0005397, the expression of hsa_circ_0005397 decreased equally when depletion of EIF4A3. Knockdown of EIF4A3 could reverse the function on HCC progression. ConclusionsHsa_circ_0005397 could promote the progression of hepatocellular carcinoma through EIF4A3. These research findings may present a novel clinical value for HCC.

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Yuan, L., Luo, M., Liu, R.-Y., Wang, H.-X., Ju, L.-L., Wang, F., Cao, L.-Y., Wang, Z.-C., Chen, L.. 2023-09-01. Hsa_circ_0005397 could promote hepatocellular carcinoma progression and metastasis through EIF4A3. https://doi.org/10.1101/2023.08.30.555568

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