MicroRNA-766-3p-mediated downregulation of HNF4G inhibits proliferation in colorectal cancer cells through the PI3K/AKT pathway
© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc..
Nuclear receptors (NRs) are a class of transcription factors that play a pivotal role in carcinogenesis, but their function in colorectal cancer (CRC) remains unclear. Here, we investigate the role NRs play in CRC pathogenesis. We found that hepatocyte nuclear factor 4 gamma (HNF4G; NR2A2), hepatocyte nuclear factor 4α (HNF4A; NR2A1), and retinoid-related orphan receptor γ (RORC; NR1F3) were significantly upregulated in CRC tissues analyzed by GEPIA bioinformatics tool. The expression of HNF4G was examined in CRC samples and cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. Increased expression of HNF4G was strongly associated with high tumor-node-metastasis stage and poor prognosis. Moreover, overexpression of HNF4G significantly promoted the proliferation of CRC cells in vitro. Next, we found that HNF4G promoted CRC proliferation via the PI3K/AKT pathway through targeting of GNG12 and PTK2. In addition, HNF4G was verified as a direct target of microRNA-766-3p (miR-766-3p). miR-766-3p inhibited the proliferation of CRC cells by targeting HNF4G in vitro and in vivo. Collectively, our study indicates that miR-766-3p reduces the proliferation of CRC cells by targeting HNF4G expression and thus inhibits the PI3K/AKT pathway. Therefore, development of therapies which target the miR-766-3p/HNF4G axis may aid in the treatment of CRC.
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E-Artikel |
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Erscheinungsjahr: |
2022 |
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Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:29 |
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Enthalten in: |
Cancer gene therapy - 29(2022), 6 vom: 22. Juni, Seite 803-813 |
Sprache: |
Englisch |
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Beteiligte Personen: |
He, Xin-Xin [VerfasserIn] |
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Links: |
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Themen: |
EC 2.7.11.1 |
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Anmerkungen: |
Date Completed 22.06.2022 Date Revised 04.02.2023 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1038/s41417-021-00362-0 |
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PPN (Katalog-ID): |
NLM327059621 |
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520 | |a Nuclear receptors (NRs) are a class of transcription factors that play a pivotal role in carcinogenesis, but their function in colorectal cancer (CRC) remains unclear. Here, we investigate the role NRs play in CRC pathogenesis. We found that hepatocyte nuclear factor 4 gamma (HNF4G; NR2A2), hepatocyte nuclear factor 4α (HNF4A; NR2A1), and retinoid-related orphan receptor γ (RORC; NR1F3) were significantly upregulated in CRC tissues analyzed by GEPIA bioinformatics tool. The expression of HNF4G was examined in CRC samples and cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. Increased expression of HNF4G was strongly associated with high tumor-node-metastasis stage and poor prognosis. Moreover, overexpression of HNF4G significantly promoted the proliferation of CRC cells in vitro. Next, we found that HNF4G promoted CRC proliferation via the PI3K/AKT pathway through targeting of GNG12 and PTK2. In addition, HNF4G was verified as a direct target of microRNA-766-3p (miR-766-3p). miR-766-3p inhibited the proliferation of CRC cells by targeting HNF4G in vitro and in vivo. Collectively, our study indicates that miR-766-3p reduces the proliferation of CRC cells by targeting HNF4G expression and thus inhibits the PI3K/AKT pathway. Therefore, development of therapies which target the miR-766-3p/HNF4G axis may aid in the treatment of CRC | ||
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