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. 2016 Mar 23:14:80.
doi: 10.1186/s12967-016-0824-x.

The association between S100A13 and HMGA1 in the modulation of thyroid cancer proliferation and invasion

Jing Zhong  1 , Chang Liu  1   2 , Ya-jun Chen  1   3 , Qing-hai Zhang  1 , Jing Yang  4 , Xuan Kang  1 , Si-Rui Chen  1 , Ge-bo Wen  1   4 , Xu-yu Zu  5 , Ren-xian Cao  6   7
Affiliations

The association between S100A13 and HMGA1 in the modulation of thyroid cancer proliferation and invasion

Jing Zhong et al. J Transl Med. .

Abstract

Background: S100A13 and high mobility group A (HMGA1) are known to play essential roles in the carcinogenesis and progression of cancer. However, the correlation between S100A13 and HMGA1 during cancer progression is not yet well understood. In this study, we determined the effects of S100A13 on HMGA1 expression in thyroid cancer cells and examined the role of HMGA1 in thyroid cancer progression.

Methods: Stable ectopic S100A13 expression TT cellular proliferation was evaluated by nude mice xenografts assays. The effect of lentivirus-mediated S100A13 knockdown on thyroid cancer cellular oncogenic properties were evaluated by MTT, colony formation assays and transwell assays in TPC1 and SW579 cells. The effect of siRNA-mediated HMGA1 knockdown on thyroid cancer cellular proliferation and invasion were evaluated by MTT, colony formation assays and transwell assays. The tissue microarray was performed to investigate the correlation between S100A13 and HMGA1 expression in tumor tissues.

Results: The ectopic expression of S100A13 could increase tumor growth in a TT cell xenograft mouse model. Moreover, lentivirus-mediated S100A13 knockdown led to the inhibition of cellular oncogenic properties in thyroid cancer cells, and HMGA1 was found to be involved in the effect of S100A13 on thyroid cancer growth and invasion. Furthermore, siRNA-mediated HMGA1 knockdown was proved to inhibit the growth of TPC1 cells and invasive abilities of SW579 cells. Clinically, it was revealed that both S100A13 and HMGA1 showed a higher expression levels in thyroid cancer cases compared with those in matched normal thyroid cases (P = 0.007 and P = 0.000); S100A13 and HMGA1 expressions were identified to be positively correlated (P = 0.004, R = 0.316) when analyzed regardless of thyroid cancer types.

Conclusions: This is the first report for the association between HMGA1 and S100A13 expression in the modulation of thyroid cancer growth and invasion. Those results would provide an essential insight into the effect of S100A13 on carcinogenesis of thyroid tumor, rending S100A13 to be potential biological marker for the diagnosis of thyroid cancer.

Keywords: HMGA1; Invasion; Proliferation; RNA interference; S100A13; Thyroid cancer.

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Figures

Fig. 1
Fig. 1
S100A13 overexpression increases tumor growth in a TT cell xenograft mouse model. a S100A13-GFP, GFP or TT groups cells were transplanted into ovariectomized athymic mice. Left mice appearances in different treated groups. Right tumor appearances in different treated groups. b Left increased tumor volume in S100A13 overexpression mice. Tumours were measured weekly using a vernier calliper and the volume was calculated according to the formula: π/6 × length × width2. Each point represents the mean ± SD for different animal measurements (n = 5) (*P < 0.05). Right increased tumor weight in S100A13 overexpression mice (**P < 0.01). c Detection of proteins expression by immunohistochemical assay of tumor tissues in nude mice in different treated groups (streptavidin biotin complex ×400)
Fig. 2
Fig. 2
a Fluorescence microscopy examination of the infection efficiencies of different lentiviral vectors in TPC1 cells (magnification ×100). I, TPC1 cells without lentiviral infection (Con group) in the light microscope; II, TPC1 cells of Con group in the fluorescence microscope; III, TPC1 cells were infected with negative lentivirus NC/GV248RNAi-LV (NC group) in the light microscope; IV, TPC1 cells of NC group in the fluorescence microscope; V, TPC1 cells were infected with lentivirus S100A13/GV248RNAi-LV#1 RNAi (KD group) at a high MOI in the light microscope; VI, TPC1 cells of KD group at a high MOI in the fluorescence microscope. b Fluorescence microscopy examination of the infection efficiencies of different lentiviral vectors in SW579 cells (magnification ×100). The description of panels was similar with that in a
Fig. 3
Fig. 3
Lentivirus-mediated S100A13 knockdown inhibited thyroid cancer cell proliferation and invasion. a Growth curves of cells in each group. MTT analysis showed that lentivirus-mediated S100A13 knockdown significantly inhibited thyroid cancer TPC1 cell proliferation (n = 3). *P < 0.05. b Colony formation assay showed that lentivirus-mediated S100A13 knockdown significantly inhibited thyroid cancer TPC1 cell colony formation (n = 3, **P < 0.01). c Transwell invasion assay showed that lentivirus-mediated S100A13 knockdown significantly inhibited thyroid cancer SW579 cell invasion. Cells were transiently transfected with lentivirus-mediated shRNA plasmids and plated on the top of the transwells. Twenty-four hours after plating, cells invaded through the pores were counted. Values are expressed as mean ± SD of three independent experiments, *P < 0.05. d Scratch-wound assay showed that lentivirus-mediated S100A13 knockdown significantly inhibited thyroid cancer SW579 cell migration. e Western blot assay showed that lentivirus-mediated S100A13 knockdown inhibited expression of HMGA1 and Snail, promoted expression of E-cadherin in SW579 cells
Fig. 4
Fig. 4
SiRNA-mediated HMGA1 knockdown inhibited thyroid cancer cell proliferation and invasion. a Growth curves of cells in each group. MTT analysis showed that siRNA-mediated HMGA1 knockdown significantly inhibited thyroid cancer TPC1 cell proliferation (n = 3). *P < 0.05. b Colony formation assay showed that siRNA-mediated HMGA1 knockdown significantly inhibited thyroid cancer TPC1 cell colony formation (n = 3, **P < 0.01). c RT-PCR and western blot assay showed that siRNA-mediated HMGA1 knockdown inhibited mRNA and protein expression of HMGA1 and Snail, promoted mRNA and protein expression of E-cadherin in thyroid cancer SW579 cell. d Transwell invasion assay showed that siRNA-mediated HMGA1 knockdown significantly inhibited thyroid cancer SW579 cell invasion. Cells were transiently transfected with HMGA1-siRNA and plated on the top of the transwells. Twenty-four hours after plating, cells invaded through the pores were counted. Values are expressed as mean ± SD of three independent experiments, **P < 0.01
Fig. 5
Fig. 5
HMGA1 overexpression affect Snail and E-candherin promoter activities in SW579 cell. a, b Luciferase activity assay showed that HMGA1 overexpression inhibited promoter activity of E-cadherin, promoted promoter activity of Snail in a dose-dependent manner
Fig. 6
Fig. 6
S100A13 and HMGA1 protein expression show a positive correlation in thyroid carcinoma (images in original magnification, ×200). a Normal thyroid tissue, b thyroid papillary carcinoma, c thyroid follicular carcinoma, d thyroid undifferentiated carcinoma
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