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lncRNA BANCR promotes the colorectal cancer metastasis through accelerating exosomes-mediated M2 macrophage polarization via regulating RhoA/ROCK signaling

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Abstract

Cancer cells-derived exosomal lncRNAs could modulate the tumorigenesis of colorectal cancer (CRC) via modulating macrophage M2 polarization. However, the clarified mechanism and function of lncRNA BANCR in CRC remains unclear. Exosomes were identified by TEM, NTA, western blot and fluorescent staining. M2 macrophages were identified by CD206 and CD163 expressions using by flow cytometry and RT-qPCR. In addition, the relation between IGF2BP2 and BANCR or RhoA were explored by RIP assay. The malignant behaviors of CRC cells were examined by CCK-8, EdU and transwell assays. Histopathological changes in mice were observed by H&E staining. Silencing of BANCR notably inhibited the proliferation, migration and invasion of CRC cells. SW620 and HCT-15 cells-derived exosomal BANCR positively regulated the macrophage M2 polarization. In addition, exosomal BANCR remarkably enhanced the promoting roles mediated by M2 macrophages on proliferation and invasion in CRC cells. Meanwhile, exosomal BANCR promoted the M2 macrophage polarization via activation of RhoA/Rock pathway by recruiting IGF2BP2. Inhibition of RhoA/Rock pathway reversed exosomal BANCR-mediated macrophages M2 polarization and CRC malignant behaviors in SW620 and HCT-15 cells. Exosomal lncRNA BANCR derived from SW620 and HCT-15 cells promoted the metastasis of CRC via inducing the polarization of M2 macrophages. Thus, BANCR might be a new target for the treatment of CRC.

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Data availability

All data generated or analysed during this study are included in this published article.

Abbreviations

CRC:

Colorectal cancer

BANCR:

BRAF-activated non-protein coding RNA

TME:

Tumor microenvironment

TAMs:

Tumor-associated macrophages

lncRNAs:

Long non-coding RNAs

lncRNAs:

Long non-coding RNAs

miRNAs:

MicroRNAs

circRNAs:

Circular RNAs

shRNA:

Short hairpin RNA

shRNA:

Short hairpin RNA

CCK-8:

Cell counting Kit-8

RIP:

RNA immunoprecipitation

IHC:

Immunohistochemical

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Acknowledgements

We would like to give our sincere gratitude to the reviewers for their constructive comments.

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Authors and Affiliations

  1. Department of General Surgery, The First Affiliated Hospital of Soochow University, Medical College of Soochow University, No.188, Shizi Street, Suzhou, 215006, Jiangsu Province, People’s Republic of China

    Ai-Xing Ding & Yu-Ting Kuang

  2. Department of General Surgery, Yancheng City No. 1 People’s Hospital, Yancheng, 224300, Jiangsu Province, People’s Republic of China

    Ai-Xing Ding, Hao Wang, Jian-Min Zhang & Wei Yang

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  1. Ai-Xing Ding
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Contributions

Ai-Xing Ding: Conceptualization, Methodology, Investigation, Visualization, Writing- Original draft preparation, Validation, Writing—Reviewing and Editing. Hao Wang: Software, Data curation. Jian-Min Zhang: Data curation. Wei Yang: Methodology. Yu-Ting Kuang: Conceptualization, Methodology, Writing- Original draft preparation, Supervision, Writing- Reviewing and Editing.

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Correspondence to Yu-Ting Kuang.

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45 pairs of CRC tumor tissues and adjacent tissues originated from Yancheng City No. 1 People’s Hospital between June 2019 and April 2021. After centrifugation, serum was collected and also plated in the condition of − 80 °C. Ethics Committee of Yancheng City No. 1 People’s Hospital approved this research. All subjects were written informed consent. The protocol was approved by the responsible governmental The ethics committee of Yancheng City No. 1 People’s Hospital approved this study.

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Ding, AX., Wang, H., Zhang, JM. et al. lncRNA BANCR promotes the colorectal cancer metastasis through accelerating exosomes-mediated M2 macrophage polarization via regulating RhoA/ROCK signaling. Mol Cell Biochem 479, 13–27 (2024). https://doi.org/10.1007/s11010-023-04709-z

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