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.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:29

Enthalten in:

Cancer gene therapy - 29(2022), 6 vom: 22. Juni, Seite 803-813

Sprache:

Englisch

Beteiligte Personen:

He, Xin-Xin [VerfasserIn]
Luo, Shan-Shan [VerfasserIn]
Qin, Hai-Quan [VerfasserIn]
Mo, Xian-Wei [VerfasserIn]

Links:

Volltext

Themen:

EC 2.7.11.1
HNF4G protein, human
Hepatocyte Nuclear Factor 4
Journal Article
MIRN766 microRNA, human
MicroRNAs
Proto-Oncogene Proteins c-akt
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 22.06.2022

Date Revised 04.02.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1038/s41417-021-00362-0

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM327059621