HNF1A regulates colorectal cancer progression and drug resistance as a downstream of POU5F1.

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • Subject Terms:
      Gene Expression Regulation, Neoplastic*; Colorectal Neoplasms/*genetics ; Drug Resistance, Neoplasm/*genetics ; Hepatocyte Nuclear Factor 1-alpha/*genetics ; Octamer Transcription Factor-3/*metabolism; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animals ; Apoptosis/genetics ; Cell Line, Tumor ; Cell Proliferation/genetics ; Chemotherapy, Adjuvant ; Colorectal Neoplasms/mortality ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/therapy ; Disease Progression ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gene Knockdown Techniques ; Glucose Transporter Type 1/genetics ; Hepatocyte Nuclear Factor 1-alpha/metabolism ; Humans ; Male ; Mice ; Middle Aged ; Primary Cell Culture ; Xenograft Model Antitumor Assays ; Young Adult
    • Abstract:
      POU5F1-expressing cells can self-renew and differentiate, contributing to metastasis formation in colorectal cancer (CRC), but it plays an important role in normal pluripotent stem cells. Here, we identified the CRC-specific gene, HNF1A, which is the downstream of POU5F1. HNF1A associates with fatty acid and glucose metabolism, and CRC cells highly expressed it. In 198 CRC patients, high HNF1A expression was an independent predictor of disease-free (P = 0.031) and overall (P = 0.007) survival. HNF1A-knockdown showed significantly reduced cell growth, increased apoptosis, and improved anticancer drug sensitivity. We revealed that HNF1A regulated controlled GLUT1 expression via HIF1A and multidrug resistance protein function to suppress SRI. HNF1A expression was elevated in persister cells after exposure to anticancer drugs, and anticancer drug sensitivity was also improved in persister cells via the inhibition of HNF1A. In conclusion, HNF1A expression can reflect resistance to anticancer drug treatment, and its suppression improves anticancer drug sensitivity as a new therapeutic target.
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    • Accession Number:
      0 (Glucose Transporter Type 1)
      0 (HNF1A protein, human)
      0 (Hepatocyte Nuclear Factor 1-alpha)
      0 (Octamer Transcription Factor-3)
      0 (POU5F1 protein, human)
      0 (SLC2A1 protein, human)
    • Publication Date:
      Date Created: 20210515 Date Completed: 20211029 Latest Revision: 20211029
    • Publication Date:
      20231215
    • Accession Number:
      PMC8121855
    • Accession Number:
      10.1038/s41598-021-89126-2
    • Accession Number:
      33990627