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LncRNA SNHG16 promotes colorectal cancer cell proliferation, migration, and epithelial–mesenchymal transition through miR-124-3p/MCP-1

Gene Therapy volume 29, pages 193–205 (2022)Cite this article

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Abstract

Colorectal cancer (CRC) has been the third leading cause of cancer-associated deaths. LncRNA SNHG16 is reported to be involved in metastasis of CRC cells. However, the mechanism by which SNHG16 regulates CRC progression is poorly understood. The proliferation of CRC cells was examined by MTT. Wound healing and transwell assay were used to measure migration and invasion ability. RT-qPCR and western blot were used to examine gene expression. Immunofluorescence was conducted to evaluate the EMT of CRC cells. Luciferase reporter assay were used to confirm direct interaction between miR-124-3p and SNHG16 or MCP-1. The interaction between miR-124-3p and SNHG16 was detected by RIP and RNA pull down assay. H&E staining was used to test the histomorphological changes of hepatic metastatic nodules. Finally, xenograft tumor experiment was utilized to determine tumor growth in vivo. SNHG16 and miR-124-3p were dysregulated in human colorectal tumors or cells. Knockdown of SNHG16 led to attenuate cell proliferation, migration, invasion, and EMT of CRC cells. And xenograft tumor experiment showed that SNHG16 might influence tumor growth. In contrast, miR-124-3p exerted the antitumor effects. Knockdown of miR-124-3p can reverse the effect of sh-SNHG16 on CRC cells. miR-124-3p could directly bind to SNHG16 or MCP-1. More importantly, MCP-1 acts as a critical effector mediating the role of SNHG16/ miR-124-3p in CRC cells. In summary, our data suggest that SNHG16 plays a contributory role in proliferation, migration, and EMT of CRC cells via miR-124-3p/MCP-1 axis, which offers a rationale for targeting SNHG16 and developing therapeutic drugs to treat CRC.

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Fig. 1: LncRNA SNHG16 is dysregulated in human colorectal tumors.
Fig. 2: Knockdown of SNHG16 attenuates proliferation, migration, invasion, and EMT of CRC cells.
Fig. 3: Knockdown of SNHG16 attenuates proliferation and metastasis of CRC cells in vivo.
Fig. 4: SNHG16 acts as a ceRNA of miR-124-3p to inhibit miR-124-3p expression and activity.
Fig. 5: miR-124-3p attenuates proliferation, migration, invasion, and EMT of CRC cells.
Fig. 6: Knockdown of miR-124-3p can reverse sh-SNHG16-triggered inhibition of proliferation, migration, invasion, and EMT of CRC cells.
Fig. 7: miR-124-3p directly targets MCP-1 and SNHG16/miR-124-3p regulates MCP-1 expression.

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Funding

This work was supported by Hunan provincial Natural Scientific Foundation [grant number 2017JJ3177] and National Natural Scientific Foundation of China [grant number 81502114].

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  1. Department of Gastroenterology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, 410005, Changsha, P.R. China

    Zhi-Yuan Chen, Xiang-Yang Wang, Yu-Ming Yang, Ming-Hao Wu, Li Yang, Duo-Ting Jiang, Hua Cai & Ya Peng

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  1. Zhi-Yuan Chen
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  8. Ya Peng
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Contributions

Z-YC and YP: guarantor of integrity of the entire study; Z-YC: study concepts, study design, manuscript preparation; X-YW: definition of intellectual content; Y-MY: literature research, manuscript editing; HC: clinical studies; YP: experimental studies, manuscript review; LY: data acquisition; M-HW: data analysis; D-TJ: statistical analysis.

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Correspondence to Zhi-Yuan Chen or Ya Peng.

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Chen, ZY., Wang, XY., Yang, YM. et al. LncRNA SNHG16 promotes colorectal cancer cell proliferation, migration, and epithelial–mesenchymal transition through miR-124-3p/MCP-1. Gene Ther 29, 193–205 (2022). https://doi.org/10.1038/s41434-020-0176-2

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