Intrabody Targeting HIF-1α Mediates Transcriptional Downregulation of Target Genes Related to Solid Tumors

Uncontrolled growth of solid tumors will result in a hallmark hypoxic condition, whereby the key transcriptional regulator of hypoxia inducible factor-1α (HIF-1α) 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-1α. After panning and screening, seven different nanobodies (Nbs) were selected, of which five were confirmed via immunoprecipitation to target the native HIF-1α 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.

Jaar van publicatie:2021

Trefwoorden:Cell Hypoxia/genetics, Down-Regulation/drug effects, Escherichia coli/genetics, Female, Gene Expression Regulation, Neoplastic, HeLa Cells, Humans, Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors, Protein Domains/genetics, Single-Domain Antibodies/genetics, Transcription, Genetic/drug effects, Transfection, Uterine Cervical Neoplasms/genetics

BOF-keylabel:ja

IOF-keylabel:ja

BOF-publication weight:1

Auteurs:International

Authors from:Higher Education

Toegankelijkheid:Open