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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Main Authors: Fei Liu, Yang Sang, Yang Zheng, Lina Gu, Lingjiao Meng, Ziyi Li, Yuyang Dong, Zishuan Wei, Cuizhi Geng, Meixiang Sang
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/14/23/5862
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author Fei Liu
Yang Sang
Yang Zheng
Lina Gu
Lingjiao Meng
Ziyi Li
Yuyang Dong
Zishuan Wei
Cuizhi Geng
Meixiang Sang
author_facet Fei Liu
Yang Sang
Yang Zheng
Lina Gu
Lingjiao Meng
Ziyi Li
Yuyang Dong
Zishuan Wei
Cuizhi Geng
Meixiang Sang
author_sort Fei Liu
collection DOAJ
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.
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spelling doaj.art-835a0855effe40f9b5c708ed31106bdc2023-11-24T10:39:53ZengMDPI AGCancers2072-66942022-11-011423586210.3390/cancers14235862circRNF10 Regulates Tumorigenic Properties and Natural Killer Cell-Mediated Cytotoxicity against Breast Cancer through the miR-934/PTEN/PI3k-Akt AxisFei Liu0Yang Sang1Yang Zheng2Lina Gu3Lingjiao Meng4Ziyi Li5Yuyang Dong6Zishuan Wei7Cuizhi Geng8Meixiang Sang9Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050017, ChinaLaboratory Animal Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050017, ChinaResearch Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050017, ChinaResearch Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050017, ChinaResearch Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050017, ChinaResearch Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050017, ChinaResearch Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050017, ChinaResearch Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050017, ChinaBreast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050017, ChinaResearch Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050017, ChinaCircular 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.https://www.mdpi.com/2072-6694/14/23/5862breast cancercircRNF10miR-934PTENNK
spellingShingle Fei Liu
Yang Sang
Yang Zheng
Lina Gu
Lingjiao Meng
Ziyi Li
Yuyang Dong
Zishuan Wei
Cuizhi Geng
Meixiang Sang
circRNF10 Regulates Tumorigenic Properties and Natural Killer Cell-Mediated Cytotoxicity against Breast Cancer through the miR-934/PTEN/PI3k-Akt Axis
Cancers
breast cancer
circRNF10
miR-934
PTEN
NK
title circRNF10 Regulates Tumorigenic Properties and Natural Killer Cell-Mediated Cytotoxicity against Breast Cancer through the miR-934/PTEN/PI3k-Akt Axis
title_full circRNF10 Regulates Tumorigenic Properties and Natural Killer Cell-Mediated Cytotoxicity against Breast Cancer through the miR-934/PTEN/PI3k-Akt Axis
title_fullStr circRNF10 Regulates Tumorigenic Properties and Natural Killer Cell-Mediated Cytotoxicity against Breast Cancer through the miR-934/PTEN/PI3k-Akt Axis
title_full_unstemmed circRNF10 Regulates Tumorigenic Properties and Natural Killer Cell-Mediated Cytotoxicity against Breast Cancer through the miR-934/PTEN/PI3k-Akt Axis
title_short circRNF10 Regulates Tumorigenic Properties and Natural Killer Cell-Mediated Cytotoxicity against Breast Cancer through the miR-934/PTEN/PI3k-Akt Axis
title_sort circrnf10 regulates tumorigenic properties and natural killer cell mediated cytotoxicity against breast cancer through the mir 934 pten pi3k akt axis
topic breast cancer
circRNF10
miR-934
PTEN
NK
url https://www.mdpi.com/2072-6694/14/23/5862
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