Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 22, Pages -Publisher
MDPI
DOI: 10.3390/ijms222212335
Keywords
HIF-1 alpha; nanobodies; transcriptional activation; target genes
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Uncontrolled growth of solid tumors can lead to hypoxic conditions and activation of HIF-1 alpha, promoting metabolism, proliferation, and metastasis of tumor cells. Inhibiting the transcriptional activity of HIF-1 could be a potential strategy for cancer therapy. Nbs selected through phage display showed significant inhibitory effects on the transcriptional activity of HIF-1, confirming their potential in cancer treatment.
Uncontrolled growth of solid tumors will result in a hallmark hypoxic condition, whereby the key transcriptional regulator of hypoxia inducible factor-1 alpha (HIF-1 alpha) will be stabilized to activate the transcription of target genes that are responsible for the metabolism, proliferation, and metastasis of tumor cells. Targeting and inhibiting the transcriptional activity of HIF-1 may provide an interesting strategy for cancer therapy. In the present study, an immune library and a synthetic library were constructed for the phage display selection of Nbs against recombinant PAS B domain protein (rPasB) of HIF-1 alpha. After panning and screening, seven different nanobodies (Nbs) were selected, of which five were confirmed via immunoprecipitation to target the native HIF-1 alpha subunit. The inhibitory effect of the selected Nbs on HIF-1 induced activation of target genes has been evaluated after intracellular expression of these Nbs in HeLa cells. The dramatic inhibition of both intrabody formats on the expression of HIF-1-related target genes has been confirmed, which indicated the inhibitory efficacy of selected Nbs on the transcriptional activity of HIF-1.
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