# A ESRP1/circPHGDH/miR-149/RAP1B positive feedback loop promotes the malignant behaviors and glycolysis of prostate cancer cell

## TL;DR

A new feedback loop involving circPHGDH, miR-149, and RAP1B promotes prostate cancer growth and spread, offering potential new treatment targets.

## Contribution

Discovery of a novel ESRP1/circPHGDH/miR-149/RAP1B feedback loop driving prostate cancer progression through glycolysis and lactylation.

## Key findings

- circPHGDH is upregulated in prostate cancer tissues and promotes cell proliferation, migration, and glycolysis.
- circPHGDH regulates miR-149, which targets RAP1B, forming a feedback loop with ESRP1 lactylation.
- Inhibiting circPHGDH suppresses tumor growth and metastasis in animal models.

## Abstract

Circular RNAs are implicated in the pathogenesis of prostate cancer (PCa). However, their functions, biogenesis and molecular mechanisms remain largely elusive. Here we aimed to investigate the role of circPHGDH in PCa. Cellular behaviors were assessed by the colony formation assay, Transwell analysis, western blotting and Seahorse assay. The underlying mechanisms were investigated using a luciferase reporter assay, RNA pull-down and real-time quantitative PCR. The lactylation of ESRP1 was examined by RNA immunoprecipitation, immunoprecipitation and western blotting. Our results revealed that circPHGDH expression was upregulated in PCa tissues and cells. Furthermore, the knockdown of circPHGDH inhibited PCa cell proliferation, migration, invasion, epithelial–mesenchymal transition and glycolysis. Mechanistically, circPHGDH functioned as a sponge for miR-149, which in turn directly targeted RAP1B. The biogenesis of circPHGDH was regulated by the splicing factor ESRP1. The glycolytic product lactate stabilized ESRP1 by promoting its lactylation at the K43 site; conversely, circPHGDH knockdown suppressed ESRP1 lactylation. Moreover, the silencing of circPHGDH inhibited tumor growth and metastasis in vivo via the miR-149/RAP1B axis, whereas circPHGDH facilitated tumor progression. In conclusion, the lactylation-modified ESRP1/circPHGDH/miR-149/RAP1B axis drives the progression of PCa. These findings provide novel insights into the pathogenesis of PCa and suggest promising therapeutic targets for its treatment.

Prostate cancer is a common disease affecting older men, but younger men are increasingly being diagnosed. Early detection is difficult because the disease often shows no symptoms until it is advanced. Current treatments such as surgery and chemotherapy help, but challenges remain owing to the cancer’s complexity and resistance to treatment. Researchers explored a molecule called circPHGDH in prostate cancer. They found that circPHGDH is more common in cancerous tissues and helps cancer cells grow and spread. The study involved analyzing tissue samples from 51 patients and conducting various lab experiments to understand how circPHGDH works. They discovered that circPHGDH interacts with other molecules such as miR-149 and RAP1B, which are involved in cancer progression. By targeting this interaction, they hope to find new ways to treat prostate cancer.

This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.