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Reduced expression of miR-30c-5p promotes hepatocellular carcinoma progression by targeting RAB32.

ABSTRACT: Hepatocellular carcinoma (HCC) remains among the most lethal of human cancers, despite recent advances in modern medicine. miR-30c-5p is frequently dysregulated in different diseases. However, the effects and the underlying mechanism of miR-30c-5p in HCC are still elusive. Here, we show that miR-30c-5p is downregulated in HCC and significantly associated with survival and tumor size in patients with HCC. We demonstrate that aberrant miR-30c-5p markedly affects HCC cell proliferation and migration. Further experiments show that RAB32 is an essential target of miR-30c-5p in HCC. These studies highlight an important role of miR-30c-5p in growth and invasion of HCC and indicate that the miR-30c-5p-RAB32 axis is an important underlying mechanism.

SUBMITTER: He Z

PROVIDER: S-EPMC8517094 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Reduced expression of miR-30c-5p promotes hepatocellular carcinoma progression by targeting RAB32.

He Zheng Z Tian Meng M Fu Xuan X

Molecular therapy. Nucleic acids 20210907

Hepatocellular carcinoma (HCC) remains among the most lethal of human cancers, despite recent advances in modern medicine. miR-30c-5p is frequently dysregulated in different diseases. However, the effects and the underlying mechanism of miR-30c-5p in HCC are still elusive. Here, we show that miR-30c-5p is downregulated in HCC and significantly associated with survival and tumor size in patients with HCC. We demonstrate that aberrant miR-30c-5p markedly affects HCC cell proliferation and migratio ...[more]

PMID: 34703646

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Project description:BackgroundHepatocellular carcinoma (HCC) is the leading cause of tumor-related death worldwide due to high morbidity and mortality, yet lacking effective biomarkers and therapies. Circular RNAs (circRNAs) are a group of non-coding RNAs that regulate gene expression through interacting with miRNAs, implicating in the tumorigenesis and progression. A novel circRNA, circTP63, was reported to be an oncogene in HCC. However, its role in HCC remains unclear.MethodsqRT-PCR was used to assess the mRNA levels of CircTP63 in 90 pairs of tumor and adjacent normal tissues from HCC patients, one human normal hepatic epithelial cell line and HCC cell lines. CCK-8, colony formation, transwell, and flow cytometry assays were performed to detect the cellular function of circTP63/miR-155-5p/ZBTB18 in HCC cells. HCC xenograft mice models were established to assess the in vivo effect of circTP63. Bioinformatic analysis, RNA pull-down and luciferase assays were used to determine the interaction among circTP63/miR-155-5p/ZBTB18.ResultscircTP63 was significantly upregulated in HCC tissues and cell lines. High circTP63 expression is closely associated with the tumor stages, lymph node metastasis, and poor prognosis of HCC patients. Functionally, knockdown of circTP63 inhibited cell proliferation, migration, invasion, and promoted cell apoptosis of HCC. Meanwhile, overexpression of circTP63 enhanced HCC progression. Mechanically, circTP63 was a sponge of miR-155-5p to facilitate the ZBTB18 expression, and the ZBTB18 expression in HCC tissues was negatively associated with the survival rate of HCC patients. Furthermore, rescued assays revealed that the reduced tumor-promoting effect on HCC cells induced by knockdown of circTP63 can be reversed by miR-155-5p inhibitor or ZBTB18 overexpression.ConclusionOur data highlight a critical circTP63-miR-155-5p-ZBTB18 regulatory network involved in the HCC progression, gaining mechanistic insights into the function of circRNAs in HCC progression, and providing effective biomarkers and therapeutic targets for HCC treatment.

Dataset Information

Reduced expression of miR-30c-5p promotes hepatocellular carcinoma progression by targeting RAB32.

Publications

Reduced expression of miR-30c-5p promotes hepatocellular carcinoma progression by targeting RAB32.

Similar Datasets

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