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Interleukin-22 promotes papillary thyroid cancer cell migration and invasion through microRNA-595/Sox17 axis

Tumor Biology volume 37, pages 11753–11762 (2016)Cite this article

Abstract

Interleukin-22 (IL-22) is an inflammatory cytokine mainly produced by activated Th17 and Th22 cells. The data presented here demonstrate that IL-22 induced the migration and invasion of papillary thyroid cancer (PTC) cells. MicroRNA expression analysis and functional studies indicated that IL-22-mediated migration and invasion is positively regulated by miR-595. Further mechanistic studies revealed that sex-determining region Y-box 17 (Sox17) is directly targeted by miR-595. We then demonstrated that IL-22 regulated migration and invasion of PTC cells via inhibiting Sox17 expression. Interestingly, in PTC cell lines and PTC tissues, expression of IL-22 and miR-595 was upregulated and Sox17 downregulated compared with normal thyroid, and their expression levels were closely correlated. Taken together, this present study suggests that IL-22 stimulation enhances the migration and invasion of PTC cells by regulating miR-595 and its target Sox17.

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Authors and Affiliations

  1. The department of Head and Neck surgery, Hubei Cancer Hospital, Wuhan, Hubei, 430079, China

    Zhidan Mei, Youhua Zhu, Kejia Jie, Daqing Fan, Jian Chen, Xiguo Liu, Liang Jiang, Qike Jia & Wei Li

  2. Animal Biosafety Level III Laboratory at the Center for Animal Experiment, State Key Laboratory of Virology, Wuhan University, Wuhan, 430071, China

    Li Zhou

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  1. Zhidan Mei
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  2. Li Zhou
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  10. Wei Li
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Correspondence to Wei Li.

Ethics declarations

All participants gave written informed consent to participate in the study. The study was conducted according to the principles of the Declaration of Helsinki and approved by the Institutional Review Board of the Hubei Cancer Hospital, in accordance with its guidelines for the protection of human subjects.

Financial support

This work was supported by research grants from the Young Scientist Fund of the National Natural Science Foundation of China (81301428) and the Fundamental Research Funds for the Central Universities (2042015kf0188).

The funding agencies had no role in study design, data collection, or analysis, decision to publish, or preparation of the manuscript.

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ESM 1

Figure S1. IL-22 can not affect the proliferation of these thyroid cancer cells. TPC-1 cells (A) and KAT-5 cells (B) were treated with rhIL-22 for 48 h at the indicated concentrations. The proliferation of the cells were quantified by MTT assay. Bar graphs represent means ± SD, n = 3 (**P < 0.01; *P < 0.05). Figure S2. IL-22 promotes the migration and invasion of KAT-5 cell. Experiments were performed as in Fig 1 except KAT-5 cells were performed. Bar graphs represent means ± SD, n = 3 Supplementary Figure 3. MicroRNA-595 is involved in IL-22 induced migration and invasion of KAT-5 cells. (A) KAT-5 cells were transfected with pre-miR-595 or control for 24 h. Then, cells were treated with or without rhIL-22 (50 ng/ml, 24 h) and allowed to migrate or invade towards serum for 24 h. (B) The experiments were performed as in (A), except the indicated anti-miR-595 or anti-miR control were used. The images shown are representative images from three independent experiments, and a statistical analysis was performed. Bar graphs represent means ± SD, n = 3 (**P < 0.01; *P < 0.05). Figure S4. MiR-595 upregulated the migration and invasion of TPC-1 cells. (A) TPC-1 cells were transfected with pre-miR-595 or control for 48 h at the indicated concentrations. The proliferation of the cells was quantified by MTT assay. (B) Experiments were performed as in A, except the indicated anti-miR-595 or anti-miR control were used. (C, D) TPC-1 cells were transfected with pre-miR-595 or control for 48 h at the indicated concentrations prior to transwell migration (C) or invasion (D) analyses. (E, F) Experiments were performed as in C and D, except the indicated anti-miR-595 or anti-miR control were used. Bar graphs represent means ± SD, n = 3. Figure S5. Sox17 is a target of miR-595. (A, B) KAT-5 cells were co-transfected with either WT or MUT Sox17 3′-UTR reporter plasmids and either pre-miR-595 (A) or anti-miR-595 (B) for 48 h prior to luciferase activity analyses. (C) KAT-5 cells were transfected with pre-miR-595 (left panel) or anti-miR-595 (right panel) for 48 h. Sox17 mRNA was quantified by real-time PCR. Bar graphs represent means ± SD, n = 3 (**P < 0.01; *P < 0.05). Figure S6. The role of Sox17 in the migration and invasion of KAT-5 cells. (A) KAT-5 cells were transfected with pCMV-Sox17 or control vector for 48 h prior to transwell migration and invasion. (B) Experiments were performed as in (A), except cells were transfected with shRNA-control or Sox17 shRNA. The images shown are representative images from three independent experiments, and a statistical analysis was performed. Bar graphs represent means ± SD, n = 3 (**P < 0.01; *P < 0.05). Figure S7. MiR-595 inhibition of KAT-5 cell migration and invasion is mediated by Sox17. Experiments were performed as in Fig 5 except KAT-5 cells were performed. Bar graphs represent means ± SD, n = 3. Table S1: Correlation of IL-22, miR-595 and Sox17 expression with clinicopathologic features in papillary thyroid cancers (PTC). Table S2: Primers Used in Real-time PCR. Table S3: The target sequence of shRNAs. Table S4: Identification of miRNAs differentially expressed in IL-22 treated TPC-1 cells. (DOC 11840 kb)

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Mei, Z., Zhou, L., Zhu, Y. et al. Interleukin-22 promotes papillary thyroid cancer cell migration and invasion through microRNA-595/Sox17 axis. Tumor Biol. 37, 11753–11762 (2016). https://doi.org/10.1007/s13277-016-5030-1

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  • DOI: https://doi.org/10.1007/s13277-016-5030-1

Keywords

  • Interleukin-22
  • miR-595
  • Sox17
  • Papillary thyroid cancer
  • Migration
  • Invasion