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LncRNA SNHG16 induces proliferation and fibrogenesis via modulating miR-141-3p and CCND1 in diabetic nephropathy

Gene Therapy volume 27, pages 557–566 (2020)Cite this article

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Abstract

LncRNAs are reported to participate in the progression of various diseases including diabetic nephropathy. Currently, we reported that SNHG16 was obviously upregulated in db/db mice and high glucose-treated mice mesangial cells. Then, functional experiments showed that SNHG16 silencing significantly inhibited proliferation of mice mesangial cells, which induced the apoptosis and triggered cell cycle arrest. Meanwhile, proliferation-related biomarkers PCNA and Cyclin D1 (CCND1) were greatly repressed. Furthermore, western blot analysis was conducted to test fibrogenesis-associated genes Fibronectin and α-SMA. Meanwhile, the increased protein expression levels of Fibronectin and α-SMA under high glucose conditions were reversed by loss of SNHG16. miR-141-3p has been reported to be involved in various diseases. Then, RNA immunoprecipitation assay revealed the relation between SNHG16 and miR-141-3p. Downregulation of SNHG16 was able to induce expression of miR-141-3p, which was obviously reduced in db/db diabetic nephropathy mice. In addition, CCND1 is a crucial cell cycle master in human diseases. CCND1 was speculated as the target of miR-141-3p and miR-141-3p inhibited CCND1 expression significantly. Meanwhile, we observed that loss of CCND1 greatly repressed mice mesangial cell proliferation and induced cell apoptosis. Taken these together, we revealed for the first time that SNHG16 induced proliferation and fibrogenesis via modulating miR-141-3p and CCND1 in diabetic nephropathy. SNHG16/miR-141-3p/CCND1 axis can suggest a pathological mechanism of progression of diabetic nephropathy.

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Fig. 1: SNHG16 was increased in db/db mice.
Fig. 2: SNHG16 was elevated in mesangial cell indicated with HG.
Fig. 3: Effect of SNHG16 on mesangial cell proliferation.
Fig. 4: Effect of SNHG16 on mesangial cells apoptosis and cell cycle.
Fig. 5: Effect of SNHG16 on mesangial cell fibrogenesis.
Fig. 6: miR-141-3p was a direct target of SNHG16.
Fig. 7: CCND1 was a direct target of miR-141-3p.

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Funding

This work was supported by the Key Program of Science and Technology Committee of Changning District, Shanghai, China, [Grant No. WKW2016 Z03].

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Author notes

  1. These authors contributed equally: Xiaohong Jiang, Qianying Ru, Ping Li

Authors and Affiliations

  1. Department of Endocrinology, Tongren Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China

    Xiaohong Jiang, Xiaoxu Ge, Kan Shao, Liuqing Xi, Bojin Xu, Qianqian Wang & Shan Huang

  2. Department of Geriatrics, Tongren Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China

    Qianying Ru

  3. Department of Hematology, Tongji Hospital of Tongji University, Shanghai, China

    Ping Li

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Contributions

SH, XJ, PL, and QR designed the study and the experiments. XJ, PL, and QR performed the experiments. XG and KS collected the data. LX, BX, and QW did the analysis. XJ drafted the manuscript. SH revised the manuscript. All of the authors finally approved the proof for submission.

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Correspondence to Shan Huang.

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Jiang, X., Ru, Q., Li, P. et al. LncRNA SNHG16 induces proliferation and fibrogenesis via modulating miR-141-3p and CCND1 in diabetic nephropathy. Gene Ther 27, 557–566 (2020). https://doi.org/10.1038/s41434-020-0160-x

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