circRNF10 Regulates Tumorigenic Properties and Natural Killer Cell-Mediated Cytotoxicity against Breast Cancer through the miR-934/PTEN/PI3k-Akt Axis

Circular RNA (circRNA), a type of non-coding RNA, has received a great deal of attention with regard to the initiation and progression of tumors. However, the molecular mechanism and function of circRNAs in breast cancer (BC) remain unclear. In the current study, we discovered that hsa_circ_0028899...

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Veröffentlicht in:Cancers 2022-11, Vol.14 (23), p.5862
Hauptverfasser: Liu, Fei, Sang, Yang, Zheng, Yang, Gu, Lina, Meng, Lingjiao, Li, Ziyi, Dong, Yuyang, Wei, Zishuan, Geng, Cuizhi, Sang, Meixiang
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container_end_page
container_issue 23
container_start_page 5862
container_title Cancers
container_volume 14
creator Liu, Fei
Sang, Yang
Zheng, Yang
Gu, Lina
Meng, Lingjiao
Li, Ziyi
Dong, Yuyang
Wei, Zishuan
Geng, Cuizhi
Sang, Meixiang
description Circular RNA (circRNA), a type of non-coding RNA, has received a great deal of attention with regard to the initiation and progression of tumors. However, the molecular mechanism and function of circRNAs in breast cancer (BC) remain unclear. In the current study, we discovered that hsa_circ_0028899 (also called circRNF10) was significantly reduced in BC tissues, and a higher level of circRNF10 was markedly related to a favorable prognosis. The results of CCK8, colony formation, Transwell, ELISA, and NK cell-mediated cytotoxicity assays indicated that increased circRNF10 expression could significantly repress the proliferation, invasion, and migration of BC cells and enhance the killing efficiency of NK cells against BC cells. According to these biological functions, the possible role and molecular mechanism of circRNF10 in BC cells were further investigated. We used bioinformatics prediction tools to predict circRNF10-bound miRNAs, which were verified by many experimental studies, including FISH, luciferase reporter assays, RIP, and Western blots. These data suggest that circRNF10 serves as a molecular sponge for miR-934 to further regulate PTEN expression and PI3k/Akt/MICA signaling in vitro and tumor growth in vivo. Altogether, these findings reveal that circRNF10 functions as a novel anti-oncogene in BC via sponging miR-934 and suppressing the PI3K/Akt/MICA pathway.
doi_str_mv 10.3390/cancers14235862
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These data suggest that circRNF10 serves as a molecular sponge for miR-934 to further regulate PTEN expression and PI3k/Akt/MICA signaling in vitro and tumor growth in vivo. 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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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However, the molecular mechanism and function of circRNAs in breast cancer (BC) remain unclear. In the current study, we discovered that hsa_circ_0028899 (also called circRNF10) was significantly reduced in BC tissues, and a higher level of circRNF10 was markedly related to a favorable prognosis. The results of CCK8, colony formation, Transwell, ELISA, and NK cell-mediated cytotoxicity assays indicated that increased circRNF10 expression could significantly repress the proliferation, invasion, and migration of BC cells and enhance the killing efficiency of NK cells against BC cells. According to these biological functions, the possible role and molecular mechanism of circRNF10 in BC cells were further investigated. We used bioinformatics prediction tools to predict circRNF10-bound miRNAs, which were verified by many experimental studies, including FISH, luciferase reporter assays, RIP, and Western blots. These data suggest that circRNF10 serves as a molecular sponge for miR-934 to further regulate PTEN expression and PI3k/Akt/MICA signaling in vitro and tumor growth in vivo. Altogether, these findings reveal that circRNF10 functions as a novel anti-oncogene in BC via sponging miR-934 and suppressing the PI3K/Akt/MICA pathway.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>36497344</pmid><doi>10.3390/cancers14235862</doi><orcidid>https://orcid.org/0000-0002-7013-0981</orcidid><oa>free_for_read</oa></addata></record>
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subjects 1-Phosphatidylinositol 3-kinase
AKT protein
Binding sites
Bioinformatics
Biotechnology
Breast cancer
Cancer therapies
Cell migration
Cell proliferation
Circular RNA
Cytotoxicity
Development and progression
Enzyme-linked immunosorbent assay
Gene expression
Killer cells
Medical prognosis
MicroRNA
MicroRNAs
Natural killer cells
Prognosis
PTEN protein
Reagents
Signal transduction
Tumors
Western blotting
title circRNF10 Regulates Tumorigenic Properties and Natural Killer Cell-Mediated Cytotoxicity against Breast Cancer through the miR-934/PTEN/PI3k-Akt Axis
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