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...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2022-11-01
|
Series: | Cancers |
Subjects: | |
Online Access: | https://www.mdpi.com/2072-6694/14/23/5862 |
_version_ | 1797463490232844288 |
---|---|
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. |
first_indexed | 2024-03-09T17:52:23Z |
format | Article |
id | doaj.art-835a0855effe40f9b5c708ed31106bdc |
institution | Directory Open Access Journal |
issn | 2072-6694 |
language | English |
last_indexed | 2024-03-09T17:52:23Z |
publishDate | 2022-11-01 |
publisher | MDPI AG |
record_format | Article |
series | Cancers |
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 |
work_keys_str_mv | AT feiliu circrnf10regulatestumorigenicpropertiesandnaturalkillercellmediatedcytotoxicityagainstbreastcancerthroughthemir934ptenpi3kaktaxis AT yangsang circrnf10regulatestumorigenicpropertiesandnaturalkillercellmediatedcytotoxicityagainstbreastcancerthroughthemir934ptenpi3kaktaxis AT yangzheng circrnf10regulatestumorigenicpropertiesandnaturalkillercellmediatedcytotoxicityagainstbreastcancerthroughthemir934ptenpi3kaktaxis AT linagu circrnf10regulatestumorigenicpropertiesandnaturalkillercellmediatedcytotoxicityagainstbreastcancerthroughthemir934ptenpi3kaktaxis AT lingjiaomeng circrnf10regulatestumorigenicpropertiesandnaturalkillercellmediatedcytotoxicityagainstbreastcancerthroughthemir934ptenpi3kaktaxis AT ziyili circrnf10regulatestumorigenicpropertiesandnaturalkillercellmediatedcytotoxicityagainstbreastcancerthroughthemir934ptenpi3kaktaxis AT yuyangdong circrnf10regulatestumorigenicpropertiesandnaturalkillercellmediatedcytotoxicityagainstbreastcancerthroughthemir934ptenpi3kaktaxis AT zishuanwei circrnf10regulatestumorigenicpropertiesandnaturalkillercellmediatedcytotoxicityagainstbreastcancerthroughthemir934ptenpi3kaktaxis AT cuizhigeng circrnf10regulatestumorigenicpropertiesandnaturalkillercellmediatedcytotoxicityagainstbreastcancerthroughthemir934ptenpi3kaktaxis AT meixiangsang circrnf10regulatestumorigenicpropertiesandnaturalkillercellmediatedcytotoxicityagainstbreastcancerthroughthemir934ptenpi3kaktaxis |