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Background <p>CircLRIG1 has been demonstrated to inhibit the progression of bladder cancer. However, the expression profile and function of circLRIG1 in colorectal cancer (CRC), the third most prevalent malignancy globally, remain to be explored.</p> Methods <p>CircLRIG1 (circBase ID: hsa_circ_0003266) expression was first analyzed in the GSE142837 dataset and subsequently validated in CRC tissues and cell lines. HT-29 and LoVo cells were subjected to gain- and loss-of-function manipulations to delineate the impact of circLRIG1 on the proliferation, migration, and apoptosis of CRC cells. RNA-binding proteins (RBPs) interacting with circLRIG1 were predicted by bioinformatic analysis, and verified by RNA pull-down and RNA immunoprecipitation assays, subcellular fractionation, and rescue experiments. Western blot and immunofluorescence were employed to assess the effects of circLRIG1 and FUS on total and phosphorylated p65 levels as well as p65 nuclear translocation. The NF-κB inhibitor PDTC was applied to circLRIG1-silenced CRC cells, and the malignant phenotypes were assessed. Finally, the tumor-suppressive capacity of circLRIG1 was evaluated in mouse subcutaneous xenograft models.</p> Results <p>CircLRIG1 was lowly expressed in CRC tissues and cell lines. Its expression was inversely correlated with advanced pathological features of CRC patients. Overexpression of circLRIG1 inhibited CRC cell proliferation, migration, and induced apoptosis. Conversely, silencing of circLRIG1 revealed the opposite effects. Mechanistically, circLRIG1 binds to FUS and inhibits its nuclear export, leading to the inactivation of NF-κB signaling. In vivo, circLRIG1 upregulation suppressed tumor growth, reduced the levels of Ki-67 and MMP9, and inhibited p65 phosphorylation.</p> Conclusions <p>CircLRIG1 inhibits CRC progression through interaction with FUS to inactivate the NF-κB pathway. This may offer a promising therapeutic strategy for CRC.</p>

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CircLRIG1 inhibits the malignant phenotypes of colorectal cancer cells by inactivating the NF-κB signaling through interaction with FUS

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月25日

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  • Qi Liu,
  • Pei Chen,
  • Lei Liu,
  • Menghui Wang,
  • Zhenjia Li

摘要

Background

CircLRIG1 has been demonstrated to inhibit the progression of bladder cancer. However, the expression profile and function of circLRIG1 in colorectal cancer (CRC), the third most prevalent malignancy globally, remain to be explored.

Methods

CircLRIG1 (circBase ID: hsa_circ_0003266) expression was first analyzed in the GSE142837 dataset and subsequently validated in CRC tissues and cell lines. HT-29 and LoVo cells were subjected to gain- and loss-of-function manipulations to delineate the impact of circLRIG1 on the proliferation, migration, and apoptosis of CRC cells. RNA-binding proteins (RBPs) interacting with circLRIG1 were predicted by bioinformatic analysis, and verified by RNA pull-down and RNA immunoprecipitation assays, subcellular fractionation, and rescue experiments. Western blot and immunofluorescence were employed to assess the effects of circLRIG1 and FUS on total and phosphorylated p65 levels as well as p65 nuclear translocation. The NF-κB inhibitor PDTC was applied to circLRIG1-silenced CRC cells, and the malignant phenotypes were assessed. Finally, the tumor-suppressive capacity of circLRIG1 was evaluated in mouse subcutaneous xenograft models.

Results

CircLRIG1 was lowly expressed in CRC tissues and cell lines. Its expression was inversely correlated with advanced pathological features of CRC patients. Overexpression of circLRIG1 inhibited CRC cell proliferation, migration, and induced apoptosis. Conversely, silencing of circLRIG1 revealed the opposite effects. Mechanistically, circLRIG1 binds to FUS and inhibits its nuclear export, leading to the inactivation of NF-κB signaling. In vivo, circLRIG1 upregulation suppressed tumor growth, reduced the levels of Ki-67 and MMP9, and inhibited p65 phosphorylation.

Conclusions

CircLRIG1 inhibits CRC progression through interaction with FUS to inactivate the NF-κB pathway. This may offer a promising therapeutic strategy for CRC.