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Background <p>MMP14 protein has been recognized to promote tumor metastasis through protease activity, yet drugs targeting the protein fail to improve survival rates, suggesting the presence of non-protein regulatory mechanisms. This study aims to explore the roles and mechanisms by which <i>MMP14</i> RNA facilitates colorectal cancer (CRC) metastasis.</p> Methods <p>Transwell assays and animal experiments utilizing loss-of-function and gain-of-function approaches were employed to assess the roles of <i>MMP14</i> RNA in facilitating CRC metastasis. A combination of immunoprecipitation assays, scRNA-seq analysis, and western blotting was conducted to elucidate the underlying mechanisms by which <i>MMP14</i> RNA promoted CRC metastasis.</p> Results <p>Our study revealed that <i>MMP14</i> RNA was highly expressed in CRC tissues and correlated with poor prognosis. The overexpression of <i>MMP14</i> RNA facilitated metastasis both in vitro and in vivo. Mechanistically, <i>MMP14</i> RNA interacted with the distal promoter of <i>STARD13</i> and bound to the N-terminal of SIRT3, facilitating its recruitment to the promoter region. This cascade of events reduced H3K27cr levels at the <i>STARD13</i> promoter, thereby inhibiting <i>STARD13</i> transcription and ultimately promoting CRC metastasis. Furthermore, we proved that silencing <i>MMP14</i> RNA had a more significant inhibitory effect on tumor metastasis compared with inhibiting the MMP14 protein.</p> Conclusions <p>The study elucidated an lncRNA-like mechanism by which <i>MMP14</i> RNA facilitated CRC metastasis via RNA-directed chromatin remodeling.</p>

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LncRNA-like MMP14 RNA facilitates colorectal cancer metastasis by suppressing H3K27cr at the STARD13 promoter region

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月6日

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  • Mengting Li,
  • Ying Gao,
  • Xiaolin Sun,
  • Wendan Zheng,
  • Mengzhen Zhang,
  • Chenlong Wang,
  • Weiwei Chu,
  • Xuemei Yang,
  • Lin Wang,
  • Maojin Zheng,
  • Wenzhi Xue,
  • Fuxing Dong,
  • Dongsheng Pei,
  • Meijian Liao

摘要

Background

MMP14 protein has been recognized to promote tumor metastasis through protease activity, yet drugs targeting the protein fail to improve survival rates, suggesting the presence of non-protein regulatory mechanisms. This study aims to explore the roles and mechanisms by which MMP14 RNA facilitates colorectal cancer (CRC) metastasis.

Methods

Transwell assays and animal experiments utilizing loss-of-function and gain-of-function approaches were employed to assess the roles of MMP14 RNA in facilitating CRC metastasis. A combination of immunoprecipitation assays, scRNA-seq analysis, and western blotting was conducted to elucidate the underlying mechanisms by which MMP14 RNA promoted CRC metastasis.

Results

Our study revealed that MMP14 RNA was highly expressed in CRC tissues and correlated with poor prognosis. The overexpression of MMP14 RNA facilitated metastasis both in vitro and in vivo. Mechanistically, MMP14 RNA interacted with the distal promoter of STARD13 and bound to the N-terminal of SIRT3, facilitating its recruitment to the promoter region. This cascade of events reduced H3K27cr levels at the STARD13 promoter, thereby inhibiting STARD13 transcription and ultimately promoting CRC metastasis. Furthermore, we proved that silencing MMP14 RNA had a more significant inhibitory effect on tumor metastasis compared with inhibiting the MMP14 protein.

Conclusions

The study elucidated an lncRNA-like mechanism by which MMP14 RNA facilitated CRC metastasis via RNA-directed chromatin remodeling.