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Paeoniflorin inhibits colorectal cancer stem cell properties via regulating LINC01711/KMT2D/KLF7 axis
1Department of Anorectal Medicine, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China.
Background:
Paeoniflorin (PF) exerts anti-tumor effects in various cancers. However, the effects of PF on colorectal cancer (CRC) are still unknown. The purpose of this study was to investigate the effects of PF on CRC.
Methods:
Message RNA (mRNA) levels were analyzed by reverse transcription quantitative polymerase chain reaction. Protein expression was determined by Western blot. Cell migration was determined by transwell assay. Cell viability was determined using cell counting kit-8. Cell proliferation was detected using colony formation and 5-ethynyl-2'deoxyuridine assay. CRC cell stem-like properties were analyzed by sphere formation assay and flow cytometry assay. The interaction between LINC01711 and lysine methyltransferase 2D (KMT2D)/KLF transcription factor 7 (KLF7) was analyzed by RNA pull-down assay. The transcription of LINC01711 was analyzed by luciferase and chromatin immunoprecipitation assays.
Results:
The results showed that PF inhibited the proliferation, migration, and stem-like behaviors of CRC cells. Moreover, PF inhibited the expression of LINC01711, which formed a turnery structure with KMT2D and KLF7. This turnery structure mediated the activation of KLF7/Wnt/β-catenin signaling. However, PF blocked the interaction between LINC01711 and KMT2D/KLF7, as well as inhibited KLF7-mediated transcription and upregulation of LINC01711. Furthermore, PF inhibited the tumor growth of CRC.
Conclusions:
Taken together, PF inhibits CRC cell proliferation and stem-like properties via blocking LINC01711/KMT2D/KLF7 axis.
Insights
Paeoniflorin (PF) inhibits colorectal cancer (CRC) cell proliferation and stem-like properties. PF blocks the LINC01711/KMT2D/KLF7 axis, reducing tumor growth in CRC.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Paeoniflorin (PF) demonstrates anti-tumor potential across various cancers.
- The specific impact of PF on colorectal cancer (CRC) remains largely unexplored.
Purpose of the Study:
- To elucidate the effects of Paeoniflorin (PF) on colorectal cancer (CRC) progression.
- To investigate the molecular mechanisms underlying PF's action in CRC.
Main Methods:
- Quantitative PCR and Western blotting assessed gene and protein expression.
- Cellular assays (Transwell, CCK-8, colony formation, EdU) evaluated proliferation and migration.
- Sphere formation and flow cytometry analyzed stem-like properties.
- RNA pull-down, luciferase, and ChIP assays investigated molecular interactions and transcription.
Main Results:
- PF significantly inhibited CRC cell proliferation, migration, and stem-like behaviors.
- PF reduced the expression of LINC01711, a key component of the KMT2D/KLF7 complex.
- PF disrupted the LINC01711/KMT2D/KLF7 interaction, inhibiting KLF7-mediated transcription and Wnt/β-catenin signaling.
- PF administration suppressed CRC tumor growth in vivo.
Conclusions:
- Paeoniflorin (PF) exerts anti-cancer effects in colorectal cancer (CRC).
- PF's mechanism involves the inhibition of the LINC01711/KMT2D/KLF7 axis.
- Targeting this axis offers a potential therapeutic strategy for CRC treatment.
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