# Transcriptomic and Functional Validation Reveals PAQR3/P6-55 as Potential Therapeutic Targets in Colon Cancer

**Authors:** Xue You, Yikuo Gai, Ziyun Wang, Yanqi Wang, Jingran Ye, Yujia Cao, Hengshuo Zhang, Ziyi Zhang, Ying Feng

PMC · DOI: 10.3390/biology14070780 · 2025-06-27

## TL;DR

This study shows that PAQR3 and its peptide P6-55 can inhibit colon cancer growth by affecting the PI3K-AKT pathway, suggesting new therapeutic targets.

## Contribution

The study identifies PAQR3 and P6-55 as novel therapeutic targets in colon cancer through functional and transcriptomic validation.

## Key findings

- P6-55, a PAQR3-derived peptide, inhibits colon cancer cell proliferation and migration in vitro and in vivo.
- PAQR3 suppresses tumor growth via the PI3K-AKT signaling pathway, as revealed by RNA sequencing.
- The therapeutic potential of PAQR3/P6-55 as colon cancer inhibitors is supported by experimental and molecular evidence.

## Abstract

This study explores the roles and therapeutic potential of Progestin and adipoQ receptor 3 (PAQR3) in colon cancer. It was found that the peptide segment P6-55, synthesized from 6 to 55 amino acids at the N-terminus of PAQR3, functions similarly to PAQR3 and effectively inhibits the growth of colon cancer both in vitro and in vivo. RNA sequencing indicated that PAQR3 suppresses tumor growth via the PI3K-AKT signaling pathway, providing a theoretical basis for therapeutic strategies targeting PAQR3/P6-55.

Colon cancer is one of the leading malignant tumors worldwide, and the membrane protein PAQR3 has been identified as a tumor suppressor in multiple cancers. Notably, the peptide synthesized from 6 to 55 amino acids at the N-terminal of PAQR3 (P6-55) has been shown to effectively inhibit the growth of gastric cancer cells. This study aims to elucidate the mechanism of PAQR3 and explore its therapeutic potential in colon cancer. CCK8 cell viability assays, colony formation assays, and transwell migration assays were employed to systematically assess the inhibitory effects of PAQR3 on the proliferation and migration of colon cancer cells. Furthermore, we confirmed that P6-55 exhibits functional similarities to PAQR3, effectively inhibiting the growth of colon cancer in vitro and in vivo. RNA sequencing revealed that PAQR3 suppresses tumor growth via the PI3K-AKT signaling pathway, providing a strong theoretical foundation for therapeutic strategies targeting PAQR3/P6-55. In conclusion, our findings highlight the therapeutic potential of PAQR3/P6-55 as novel colon cancer inhibitors.

## Linked entities

- **Genes:** PAQR3 (progestin and adipoQ receptor family member 3) [NCBI Gene 152559]
- **Proteins:** PAQR3 (progestin and adipoQ receptor family member 3)
- **Diseases:** colon cancer (MONDO:0002032), gastric cancer (MONDO:0001056)

## Full-text entities

- **Genes:** PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, PAQR3 (progestin and adipoQ receptor family member 3) [NCBI Gene 152559] {aka RKTG}
- **Diseases:** gastric cancer (MESH:D013274), Colon Cancer (MESH:D015179), cancers (MESH:D009369)
- **Chemicals:** P6-55 (-)
- **Cell lines:** CCK8 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_2873)

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12292340/full.md

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Source: https://tomesphere.com/paper/PMC12292340