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Background <p>Our previous research revealed that PRDI-BF1 and RIZ homology domain containing protein 14 (PRDM14) accelerated human non-small cell lung cancer (NSCLC) cell migration. However, the internal mechanism remains unclear.</p> Objective <p>Herein, we aimed to explore whether PRDM14 modulates NSCLS cell growth and metastasis via H3K27me3-mediated phosphatidylethanolamine-binding protein 1 (PEBP1)/Raf-1/MEK/ERK signaling.</p> Methods <p>PRDM14 overexpression plasmid (OE-PRDM14), siRNA targeting PRDM14 (si-PRDM14) or si-jumonji domain-containing protein 3 (si-JMJD3) were transfected to alter PRDM14 or JMJD3 expressions. Vemurafenib (VMF) was utilized to inhibit Raf-1/MEK/ERK signaling. Cell proliferation was tested via Edu staining and colony formation assay. Cell migration and invasion were evaluated through two-chamber transwell assay. The protein levels of polycomb repressive complex 2 (PRC2), tri-methylation at lysine 27 of histone H3 (H3K27me3) and PEBP1/Raf-1/MEK/ERK signaling were measured via western blotting. qPCR was used to test mRNA expressions of PEBP1, c-Fos, c-Jun and c-Myc.</p> Results <p>OE-PRDM14 promoted A549 cell proliferation, migration and invasion, elevated PRC2 and H3K27me3 expressions, lowered PEBP1 expression and activated Raf-1/MEK/ERK signaling. si-PRDM14 had contrary influences. VMF weakened the influences of OE-PRDM14 on A549 cell functions and Raf-1/MEK/ERK signaling, but had no significant effects on PEBP1 and H3K27me3 levels. si-JMJD3 accelerated the influences of PRDM14 overexpression on A549 cell functions, PEBP1 and H3K27me3 expressions, as well as Raf-1/MEK/ERK signaling.</p> Conclusions <p>PRDM14 promoted NSCLC proliferation, migration and invasion via modulating PRC2/H3K27me3-mediated PEBP1/Raf-1/MEK/ERK signaling activation. PRDM14 might be as a new target in NSCLC therapy.</p>

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PRDM14 promoted NSCLC cell proliferation, migration and invasion via modulating H3K27me3-mediated PEBP1/Raf-1/MEK/ERK MAPK signaling

  • 期刊论文

  • 发表日期：

    2025年8月26日

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  • He Shi,
  • Yunfei Jiang,
  • Haijun Mu,
  • Guohua Liu,
  • Xinyue Cheng,
  • Weili Kong,
  • Xingqi Zhou,
  • Xiaoqiang Wen,
  • Xiao Wang,
  • Yiyu Lin,
  • Linyu Pan,
  • Haiying Dong,
  • Hongxia Bi,
  • Lina He,
  • Hongyan Zheng,
  • Hanbing Shi

摘要

Background

Our previous research revealed that PRDI-BF1 and RIZ homology domain containing protein 14 (PRDM14) accelerated human non-small cell lung cancer (NSCLC) cell migration. However, the internal mechanism remains unclear.

Objective

Herein, we aimed to explore whether PRDM14 modulates NSCLS cell growth and metastasis via H3K27me3-mediated phosphatidylethanolamine-binding protein 1 (PEBP1)/Raf-1/MEK/ERK signaling.

Methods

PRDM14 overexpression plasmid (OE-PRDM14), siRNA targeting PRDM14 (si-PRDM14) or si-jumonji domain-containing protein 3 (si-JMJD3) were transfected to alter PRDM14 or JMJD3 expressions. Vemurafenib (VMF) was utilized to inhibit Raf-1/MEK/ERK signaling. Cell proliferation was tested via Edu staining and colony formation assay. Cell migration and invasion were evaluated through two-chamber transwell assay. The protein levels of polycomb repressive complex 2 (PRC2), tri-methylation at lysine 27 of histone H3 (H3K27me3) and PEBP1/Raf-1/MEK/ERK signaling were measured via western blotting. qPCR was used to test mRNA expressions of PEBP1, c-Fos, c-Jun and c-Myc.

Results

OE-PRDM14 promoted A549 cell proliferation, migration and invasion, elevated PRC2 and H3K27me3 expressions, lowered PEBP1 expression and activated Raf-1/MEK/ERK signaling. si-PRDM14 had contrary influences. VMF weakened the influences of OE-PRDM14 on A549 cell functions and Raf-1/MEK/ERK signaling, but had no significant effects on PEBP1 and H3K27me3 levels. si-JMJD3 accelerated the influences of PRDM14 overexpression on A549 cell functions, PEBP1 and H3K27me3 expressions, as well as Raf-1/MEK/ERK signaling.

Conclusions

PRDM14 promoted NSCLC proliferation, migration and invasion via modulating PRC2/H3K27me3-mediated PEBP1/Raf-1/MEK/ERK signaling activation. PRDM14 might be as a new target in NSCLC therapy.