PIN1 transcript variant 2 acts as a long non-coding RNA that controls the HIF-1-driven hypoxic response

Area of Science:

• Molecular Biology
• Gene Regulation
• Cancer Biology

Background:

• Hypoxia-Inducible Factor 1 (HIF-1) is crucial for cellular adaptation to low oxygen conditions.
• The prolyl isomerase Pin1's role in regulating HIF-1α has been debated.
• Previous studies suggested Pin1 protein regulates HIF-1α, but the mechanism remained unclear.

Purpose of the Study:

• To elucidate the precise mechanism by which Pin1 influences HIF-1α expression.
• To investigate the role of PIN1 transcripts in regulating HIF-1α.
• To clarify the controversial role of Pin1 in hypoxia response.

Main Methods:

• Utilized small interfering RNAs (siRNAs) to silence PIN1 transcripts and Pin1 protein.
• Performed gene expression analysis to quantify HIF-1α and its target genes.
• Investigated the effect of PIN1 transcript variants on HIF1A gene transcription.

Main Results:

• Silencing PIN1 transcripts, particularly PIN1-v2, upregulated hypoxia-induced HIF-1α expression.
• Overexpression of Pin1 protein did not inhibit HIF-1α under hypoxia.
• PIN1-v2, a long non-coding RNA, was identified as the key regulator, inhibiting HIF1A gene transcription.

Conclusions:

• The PIN1 transcript variant 2 (PIN1-v2) acts as a long non-coding RNA that downregulates HIF-1α.
• PIN1-v2 inhibits HIF1A gene transcription, thereby modulating HIF-1 pathway activity.
• This discovery provides a new perspective on the regulation of hypoxia response by non-coding RNAs.