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. 2022 Jun 23;21:135. doi: 10.1186/s12943-022-01600-1

Fig. 5.

Fig. 5

CRC has a HIF1A-RRAGB-mTORC1 positive feedback loop that is antagonized by circEXOC6B. A RT-qPCR showed a positive relationship between HIF1A and RRAGB expression in six CRC cell lines. B RT-qPCR indicated the expression levels of HIF1A and RRAGB were positively correlated in 26 CRC tissues. C RT-qPCR was performed to detect the expression of RRAGB and HIF1A mRNA after knockdown of HIF1A or overexpression of RRAGB in SW620 and HCT116. D The promoter region of RRAGB contained three HREs and ChIP assay indicated that HIF1A bound to the second HRE site of the promoter. E Dual-luciferase reporter assay confirmed that HIF1A bound to the second HRE site of RRAGB promoter and promoted luciferase transcription. Wt: wild HRE, Mut: mutant HRE. F HIF1A activator ML228 was used to upregulate HIF1A expression, and western blotting showed that the RRAGB level was increased. However, the effect could be abrogated by circEXOC6B. G Overexpression of circEXOC6B downregulated RRAGB expression. H Knockdown of circEXOC6B elevated RRAGB expression. I IHC showed that subcutaneous tumors with stable silencing of circEXOC6B expression had higher expression of RRAGB than the control group. Scale: 20 μm