FUNDC2, a mitochondrial outer membrane protein, mediates triple-negative breast cancer progression via the AKT/GSK3ß/GLI1 pathway.

Triple-negative breast cancer (TNBC) lacks effective therapeutic targets and has a poor prognosis, easy recurrence and metastasis. It is urgent and important to explore TNBC treatment targets. Through mass spectrometry combined with qRT-PCR validation in luminal A cells and TNBC cells, high-content screening and clinical sample analysis, FUNDC2 was discovered as a novel target. The function of the outer mitochondrial membrane protein FUNDC2 in breast cancer is still unclear. In this study, we find that FUNDC2 expression in TNBC tissues is significantly higher than that in luminal subtype breast cancer tissues. FUNDC2 silencing in TNBC cells significantly reduces cell proliferation, migration and invasion. As demonstrated in vivo using subcutaneous tumor xenografts in mice, FUNDC2 suppression significantly inhibits tumor growth. The underlying mechanism might be mediated by inactivating its downstream signal AKT/GSK3ß and GLI1, a key factor of the Hedgehog signaling pathway. Therefore, FUNDC2 may promote TNBC progression and provide a therapeutic target for treating TNBC.

CPNE1 mediates glycolysis and metastasis of breast cancer through activation of PI3K/AKT/HIF-1α signaling.

CPNE1 regulates multiple signaling pathways and can stimulate cell proliferation and differentiation by activating the AKT-mTOR signaling pathway. In addition, CPNE1 is associated with various cancers; however, its role in breast cancer, particularly in TNBC, has not been fully elucidated. Our study aimed to reveal the impact of the CPNE1/PI3K/AKT/HIF-1α axis on TNBC. We first measured the expression of CPNE1 in the tumor tissues of TNBC patients and examined its prognostic value. Subsequently, we used sh-CPNE1 and overexpression vectors to transfect TNBC cell lines and analyzed cell viability, migration, and invasive abilities using colony formation and CCK-8 assays. Metabolites were analyzed through metabolomics. We found that higher expression of CPNE1 predicted poor prognosis in TNBC patients. Knockdown of CPNE1 reduced the viability, migration, invasion, and proliferation capabilities of TNBC cells. Furthermore, metabolomics analysis showed that glucose metabolism was the most dominant pathway, and knockdown of CPNE1 significantly limited the glycolytic activity of TNBC cells. We verified these conclusions in mouse models. Additionally, we overexpressed CPNE1 and treated TNBC cell lines with a PI3K inhibitor (LY294002). The results indicated that CPNE1 promoted aerobic glycolysis in TNBC cells through the PI3K/AKT/HIF-1α signaling pathway. This suggests that CPNE1 regulates cell glycolysis and participates in the development of TNBC. Our study may provide a new therapeutic target for TNBC treatment.

CBX7 regulates metastasis of basal-like breast cancer through Twist1/EphA2 pathway.

BACKGROUND: Basal-like breast cancer (BLBC) is an important subtype of breast cancer. Twist1 is a key transcription factor in BLBC metastasis, which serves a key role in tumorigenesis. The potential mechanism of Twist1 in BLBC remains to be elucidated. Here, we explored the role and molecular mechanism of Twist1 in BLBC. METHODS: The levels of CBX7, Twist1 and EphA2 in BLBC tissues and cells were determined by Western blot. ChIP and dual-luciferase reporter assays confirmed the interaction between CBX7, Twist1 and EphA2 promoter. The cellular functions were analyzed by CCK-8, colony formation, wound healing and Transwell assays. Expression of EMT related proteins was analyzed by Western blot. IHC measured the expression of CBX7, Twist1 and EphA2 in tumor tissues. RESULTS: CBX7 was down-regulated in BLBC tissues and cells, whereas Twist1 and EphA2 were up-regulated. Twist1 silencing inhibited the cell migration, invasion and cancer metastasis of BLBC through targeting EphA2 and regulating EphA2 expression. Additionally, CBX7 blocked the binding of Twist1 to EphA2 promoter and inhibited EphA2 expression and suppressed BLBC growth and metastasis via Twist1/EphA2 axis. CONCLUSION: CBX7 suppresses BLBC growth and metastasis through Twist1/EphA2 pathway. Our study may provide evidence and new therapeutic targets for the comprehensive treatment of BLBC.

ox-LDL induces autophagy-mediated apoptosis by suppressing secretagogin-regulated autophagic flux in pancreatic ß-cells.

Lipotoxicity has been shown to induce the loss of functional ß-cell mass and lead to type 2 diabetes, but the mechanism remains unknown. In this study, we aim to explore the role of secretagogin (SCGN) in lipotoxicity-induced ß-cell injury. Our results indicate that ox-LDL treatment leads to autophagic cell death, as evidenced by decreased cell viability, aggravated cell apoptosis, and the accumulation of the p62 protein in MIN6 cells. LysoTracker Red staining, TEM and mRFP-GFP-LC3 assays demonstrate that autophagic flux is blocked in ox-LDL-treated MIN6 cells. Intriguingly, SCGN is significantly decreased in MIN6 cells under lipotoxic conditions. Additionally, siRNA-guided SCGN knockdown blocks autophagic flux triggered by rapamycin, while SCGN restoration alleviates autophagic flux retardation and mitigates cell apoptosis. The physical interaction between SCGN and SNAP29 is validated by bioinformatics analysis, coimmunoprecipitation assay and SCGN knockdown test. Downregulation of SCGN expression reduces the interaction of these two proteins. Taken together, our results indicate that ox-LDL treatment induces apoptotic ß-cell death by blocking autophagic flux dependent on SCGN downregulation. SCGN administration prevents lipotoxic ß-cell injury and may be a potential therapeutic strategy to promote ß-cell expansion in type 2 diabetes.

Erratum: Twist promotes tumor metastasis in basal-like breast cancer by transcriptionally upregulating ROR1: Erratum.

[This corrects the article DOI: 10.7150/thno.21477.].

A novel secretagogin/ATF4 pathway is involved in oxidized LDL-induced endoplasmic reticulum stress and islet ß-cell apoptosis.

Excessive accumulation of cholesterol in ß cells initiates endoplasmic reticulum (ER) stress and associated apoptosis. We have reported that excessive uptake of cholesterol by MIN6 cells decreases the expression of secretagogin (SCGN) and then attenuates insulin secretion. Here, we aimed to determine whether cholesterol-induced SCGN decrease is involved in the modulation of ER stress and apoptosis in pancreatic ß cells. In this study, MIN6 cells were treated with oxidized low-density lipoprotein (ox-LDL) for 24 h, and then intracellular lipid droplets and cell apoptosis were quantified, and SCGN and ER stress markers were identified by western blot analysis. Furthermore, small interfer RNA (siRNA)-mediated SCGN knockdown and recombinant plasmid-mediated SCGN restoration experiments were performed to confirm the role of SCGN in ER stress and associated cell apoptosis. Finally, the interaction of SCGN with ATF4 was computationally predicted and then validated by a co-immunoprecipitation assay. We found that ox-LDL treatment increased the levels of ER stress markers, such as phosphorylated protein kinase-like endoplasmic reticulum kinase, phosphorylated eukaryotic initiation factor 2 alpha, activating transcription factor 4 (ATF4), and transcription factor CCAAT-enhancer-binding protein homologous protein, and promoted MIN6 cell apoptosis; in addition, the expression of SCGN was downregulated. siRNA-mediated SCGN knockdown exacerbated ß-cell ER stress by increasing ATF4 expression. Pretreatment of MIN6 cells with the recombinant SCGN partly antagonized ox-LDL-induced ER stress and apoptosis. Furthermore, a co-immunoprecipitation assay revealed an interaction between SCGN and ATF4 in MIN6 cells. Taken together, these results demonstrated that pancreatic ß-cell apoptosis induced by ox-LDL treatment can be attributed, in part, to an SCGN/ATF4-dependent ER stress response.

Therapeutic activity of DCC-2036, a novel tyrosine kinase inhibitor, against triple-negative breast cancer patient-derived xenografts by targeting AXL/MET.

Triple-negative breast cancer (TNBC) is insensitive to endocrine therapies and targeted therapies to human epidermal growth factor receptor-2 (HER2), estrogen receptor (ER) and progesterone receptor (PR). New targets and new targeted therapeutic drugs for TNBC are desperately needed. Our study confirmed that DCC-2036 inhibited the proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of TNBC cells as well as induced apoptosis. Moreover, the antiproliferative activity of DCC-2036 was more efficient than that of most clinical drugs. In addition, the combination of DCC-2036 and cisplatin or lapatinib had synergistic effects on TNBC cells. Mechanistically, DCC-2036 targeted AXL/MET, especially AXL, and regulated the downstream PI3K/Akt-NFκB signaling to exert its antitumor effect in TNBC. DCC-2036 also inhibited the growth and metastasis of xenografted MDA-MB-231 cells (AXL/MET-high TNBC cells) but not MDA-MB-468 cells (AXL-low TNBC cells) in NSG mice in vivo. Furthermore, DCC-2036 significantly inhibited tumor growth and invasion of AXL/MET-high TNBC PDX tumors but not AXL/MET-low TNBC PDX tumors. These results highlighted the roles of AXL/MET in cancer growth and metastasis and further verified that the critical targets of DCC-2036 are AXL and MET, especially AXL. In addition, there was no significant toxicity of DCC-2036 even at a high dosage. Therefore, DCC-2036 may be a potential compound to treat TNBC, especially for tumors with AXL/MET overexpression.

Twist promotes tumor metastasis in basal-like breast cancer by transcriptionally upregulating ROR1.

Rationale: Twist is a key transcription factor for induction of epithelial-mesenchymal transition (EMT), which promotes cell migration, invasion, and cancer metastasis, confers cancer cells with stem cell-like characteristics, and provides therapeutic resistance. However, the functional roles and targeted genes of Twist in EMT and cancer progression remain elusive. Methods: The potential targeted genes of Twist were identified from the global transcriptomes of T47D/Twist cells by microarray analysis. EMT phenotype was detected by western blotting and immunofluorescence of marker proteins. The dual-luciferase reporter and chromatin immunoprecipitation assays were employed to observe the direct transcriptional induction of ROR1 by Twist. A lung metastasis model was used to study the pro-metastatic role of Twist and ROR1 by injecting MDA-MB-231 cells into tail vein of nude mice. Bio-informatics analysis was utilized to measure the metastasis-free survival of breast cancer patients. Results: Twist protein was proved to directly activate the transcription of ROR1 gene, a receptor of Wnt5a in non-canonical WNT signaling pathway. Silencing of ROR1 inhibited EMT process, cell migration, invasion, and cancer metastasis of basal-like breast cancer (BLBC) cells. Knockdown of ROR1 also ameliorated the pro-metastatic effect of Twist. Furthermore, analyses of clinical specimens indicated that high expression of both ROR1 and Twist tightly correlates with poor metastasis-free survival of breast cancer patients. Conclusion: ROR1 is a targeted gene of Twist. Twist/ROR1 signaling is critical for invasion and metastasis of BLBC cells.

HMGA1 Mediated High-Glucose-Induced Vascular Smooth Muscle Cell Proliferation in Diabetes Mellitus: Association Between PI3K/Akt Signaling and HMGA1 Expression.

High-mobility group protein A1 (HMGA1), an architectural transcription factor, was found to regulate multiple gene expression in mammals. Recent studies firmly indicate an association between HMGA1 and type 2 diabetes. However, the presence and function of HMGA1 in diabetic vasculopathy has not been substantiated. in this study, we first determined the HMGA1 changes in aorta tissue of diabetic rats. In streptozotocin-induced diabetic rats, a higher level of blood glucose and plasma lipids, an increase of intima-media thickness, and a significant upregulation and accumulation of HMGA1, mainly in the nucleus and around the nuclear membrane of vascular smooth muscle cells (VSMCs), were detected. In vitro, high glucose increased HMGA1 expression and promoted proliferation of VSMCs, which could be blunted by Wortmannin and LY294002, inhibitors of PI3K/Akt pathway, and specificity protein 1 (SP1) siRNA. Moreover, knockdown of HMGA1 could weaken the upregulation of cyclin D1 accompanied by high-glucose-induced HMGA1 in VSMCs. Taken together, these findings demonstrate the vital role of PI3K/Akt-SP1-HMGA1 pathway in high-glucose-induced VSMCs proliferation.

Protein arginine N-methyltransferase 2 reverses tamoxifen resistance in breast cancer cells through suppression of ER-α36.

Breast cancer is one of the most common malignancies in females, and 17ß-estradiol (E2)/estrogen receptor α (ERα) signaling plays an important role in the initiation and progression of breast cancer. The role of the ER-α subtype and its co-regulator in the initiation of breast cancer and the occurrence of tamoxifen resistance remains to be further elucidated. In our previous studies, protein arginine N-methyltransferase 2 (PRMT2), a co-regulator of estrogen receptor-α (ER-α), was confirmed to interact with ER-α66 and has the ability to inhibit cell proliferation in breast cancer cells. In the present study, we found that tamoxifen treatment induced a decrease in PRMT2 and an increase in ER-α36 as well as ER-α36-mediated non-genomic effect in MDA-MB-231 cells, which were relatively resistant to tamoxifen by contrast to MCF-7 cells. Moreover, PRMT2 was able to interact with ER-α36 directly, suppress ER-α36 and downstream PI3K/Akt and MAPK/ERK signaling, reversing the tamoxifen resistance of breast cancer cells. The present study may be meaningful for understanding the role of PRMT2 in breast cancer progression and for developing a new endocrine therapeutic strategy for breast cancer patients with tamoxifen resistance.

Negative feedback loop between ZBTB7A and TGF-ß in breast cancer.

Zinc finger and BTB domain containing 7A (ZBTB7A) is aberrantly expressed in breast cancer, but the involvement of ZBTB7A in breast cancer remains controversial. Transforming growth factor-ß (TGF-ß) is a pleiotropic cytokine which promotes breast cancer metastasis. ZBTB7A and TGF-ß are important factors in tumor development. However, the association between ZBTB7A and TGF-ß in breast cancer remains unknown. The results of the present study revealed that TGF-ß1 induced the expression of ZBTB7A via the phosphoinositide 3-kinase-protein kinase B signaling pathway in human breast cancer cells, and ZBTB7A inhibited the expression of TGF-ß1 through indirectly suppressing the promoter activity of TGF-ß1. Furthermore, no significant correlation between the expression of ZBTB7A and TGF-ß1 were identified in breast cancer tissues using tissue microarray assay and human cancer genomics analysis. These results have identified a negative feedback loop between ZBTB7A and TGF-ß signaling, suggesting ZBTB7A as a potential modulator of breast cancer metastasis. Thus, the results of the present study suggested that ZBTB7A is a potential prognostic biomarker for breast cancer.

PRMT2ß, a C-terminal splice variant of PRMT2, inhibits the growth of breast cancer cells.

Our previous study reported several alternative splicing variants of arginine N-methyltransferase 2 (PRMT2), which lose different exons in the C-terminals of the wild-type PRMT2 gene. Particularly, due to frame-shifting, PRMT2ß encodes a novel amino acid sequence at the C-terminus of the protein, the function of which is not understood. In the present study, we determined the role of PRMT2ß in breast cancer cell proliferation, apoptosis and its effect on the Akt signaling pathway. Stable breast cancer MCF7 cell line with lentivirus-mediated PRMT2ß overexpression was obtained after selection by puromycin for 2 weeks. The effect of lentivirus-mediated PRMT2ß overexpression on breast cancer cellular oncogenic properties was evaluated by MTT, colony formation, cell cycle analysis and apoptosis assays in MCF7 cells. Luciferase activity assay and western blot analysis were performed to characterize the effects of PRMT2ß on cyclin D1 promoter activities and the Akt signaling pathway. Tissue microarray was performed to investigate the association of PRMT2ß with breast cancer progression. Lentivirus-mediated PRMT2ß overexpression suppressed the cell proliferation and colony formation of breast cancer MCF7 cells. PRMT2ß overexpression induced cell cycle arrest and apoptosis of MCF7 cells. Furthermore, PRMT2ß was revealed to suppress the transcription activity of the cyclin D1 promoter, and PRMT2ß was also found to inhibit cyclin D1 expression via the suppression of Akt/GSK-3ß signaling in breast cancer cells. Clinically, it was revealed that PRMT2ß expression was negatively correlated with human epidermal growth factor receptor 2 (HER2) (p=0.033) in breast tumors. Our results revealed that PRMT2ß, a novel splice variant of PRMT2, plays potential antitumor effect by suppressing cyclin D1 expression and inhibiting Akt signaling activity. This also opens a new avenue for treating breast cancer.

TGF-ß1 induces HMGA1 expression: The role of HMGA1 in thyroid cancer proliferation and invasion.

The role of transforming growth factor-ß1 (TGF-ß1) is complicated and plays a different role in the development of cancer. High mobility group A (HMGA1) participates in multiple cellular biology processes, and exerts important roles in the epithelial-mesenchymal transition (EMT). However, the correlation of TGF-ß1 and HMGA1 in cancer cells is not yet fully understood. In this study, we determined the effects of TGF-ß1 on HMGA1 expression in thyroid cancer cells and examined the role of HMGA1 in thyroid cancer progression. With real-time PCR and immunofluorescence staining, our study demonstrated that TGF-ß1 induced the expression of HMGA1 through phosphoinositide 3-kinase (PI3K) and the extracellular signal-related kinase (ERK) signaling in thyroid cancer cells. With luciferase reported assay, the HMGA1 promoter activity was activated by TGF-ß1 in the SW579 cells. Furthermore, lentivirus-mediated HMGA1 knockdown inhibits cellular oncogenic properties of thyroid cancer cells. Clinically, tissue microarray revealed that HMGA1 was expressed in thyroid carcinoma more than that in normal thyroid tissues (P<0.001); expression of HMGA1 and MMP-2 was identified to be positively correlated (P=0.017). The present study established the first link between HMGA1 and TGF-ß1 in the regulation of thyroid cancer proliferation and invasion, and provided evidence for the pivotal role of HMGA1 in the progression of thyroid cancer, indicating HMGA1 to be potential biological marker for the diagnosis of thyroid cancer.

MicroRNA-32 promotes calcification in vascular smooth muscle cells: Implications as a novel marker for coronary artery calcification.

Cardiovascular calcification is one of the most severe outcomes associated with cardiovascular disease and often results in significant morbidity and mortality. Previous reports indicated that epigenomic regulation of microRNAs (miRNAs) might play important roles in vascular smooth muscle cell (VSMC) calcification. Here, we identified potential key miRNAs involved in vascular calcification in vivo and investigated the role of miR-32-5p (miR-32). According to microarray analysis, we observed increased expression of miR-125b, miR-30a, and miR-32 and decreased expression of miR-29a, miR-210, and miR-320 during the progression of vascularcalcification. Additionally, gain- and loss-of-function studies of miR-32 confirmed promotion of VSMC calcification in mice through the enhanced expression of bonemorphogenetic protein-2, runt-related transcription factor-2(RUNX2), osteopontin, and the bone-specific phosphoprotein matrix GLA protein in vitro. Moreover, miR-32 modulated vascularcalcification progression by activating phosphoinositide 3-kinase (PI3K)signaling and increasing RUNX2 expression and phosphorylation by targeting the 3'-untranslated region of phosphatase and tensin homolog Mrna (PTEN) in mouse VSMCs. Furthermore, we detected higher miR-32 levels in plasmafrom patients with coronary artery disease with coronary artery calcification (CAC) as compared with levels observed in non-CAC patients (P = 0.016), further confirming miR-32 as a critical modulator and potential diagnostic marker for CAC.

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

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.

TGF-ß1 induces HMGA1 expression in human breast cancer cells: implications of the involvement of HMGA1 in TGF-ß signaling.

Transforming growth factor-ß1 (TGF-ß1) signaling and high mobility group A (HMGA1) are known to play essential roles in the progression of breast cancer by inducing epithelial-mesenchymal transition. However, the correlation between TGF-ß1 and HMGA1 in breast cancer cell is not yet well understood. In this study, we determined the effects of TGF-ß1 on HMGA1 expression in breast cancer cells and examined the role of HMGA1 in breast cancer progression. Our results demonstrated that TGF-ß1 induced the expression of HMGA1 in both MCF-7 and MDA-MB-231 breast cancer cells, as shown by RT-qPCR and immunofluorescence staining; however, the TGF-ß1-induced expression of HMGA was blocked by treatment of the cells with phosphatidylinositol-3 kinase (PI3K) signaling inhibitors. Moreover, the HMGA1 promoter activity was found to be activated by TGF-ß1 in the MCF-7 and MDA-MB-231 cells and we found that specificity protein 1 (Sp1) was involved in the TGF-ß1-induced HMGA1 promoter activity, as shown by luciferase activity assay. Furthermore, the enforced expression of HMGA1 by transfection with a HMGA1 promoter enhanced cellular oncogenic properties, including proliferation, migration and invasion, and a tissue microarray revealed that breast tumors expressing human epidermal growth factor receptor 2 (HER2) showed higher expression levels of HMGA1 (P=0.007). In addition, higher HMGA1 expression levels were also observed in the ductal breast cancer cases compared with the lobular breast cancer cases (P=0.000). These findings establish the first link between HMGA1 and TGF-ß1 in breast cancer, providing further evidence of the pivotal role of HMGA1 in breast cancer progression.

Proliferating pancreatic beta-cells upregulate ALDH.

High levels of aldehyde dehydrogenase (ALDH) activity have been regarded as a specific feature of progenitor cells and stem cells. Hence, as an indicator of ALDH activity, aldefluor fluorescence has been widely used for the identification and isolation of stem and progenitor cells. ALDH activity was recently detected in embryonic mouse pancreas, and specifically and exclusively in adult centroacinar and terminal duct cells, suggesting that these duct cells may harbor cells of endocrine and exocrine differentiation potential in the adult pancreas. Here, we report the presence of aldefluor+ beta-cells in a beta-cell proliferation model, partial pancreatectomy. The aldefluor+ beta-cells are essentially all positive for Ki-67 and expressed high levels of cell-cycle activators such as CyclinD1, CyclinD2, and CDK4, suggesting that they are mitotic cells. Our data thus reveal a potential change in ALDH activity of proliferating beta-cells, which provides a novel method for the isolation and analysis of proliferating beta-cells. Moreover, our data also suggest that aldefluor lineage-tracing is not a proper method for analyzing progenitor or stem activity in the adult pancreas.

Wnt/ß-catenin signaling pathway and lipolysis enzymes participate in methylprednisolone induced fat differential distribution between subcutaneous and visceral adipose tissue.

Glucocorticoids (GCs) are well known to induce fat distribution, which is consistent with the central adiposity phenotype seen in Cushing's syndrome. GCs have been proposed to be both adipogenic and lipolytic in action within adipose tissues. Different adipogenic and lipolytic effects between subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) are likely to play a role in GCs induced fat differential distribution. Wnt/ß-catenin signaling pathway is one of the most important regulators in adipogenesis. Adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL) are the major lipases contributing to lipolysis. In the present study, we measured fat depot masses and the expression of Wnt/ß-catenin signaling pathway and lipolytic enzymes of female Sprague-Dawley rats treated with or without methylprednisolone. We assessed the roles of Wnt/ß-catenin signaling pathway and lipolytic enzymes in fat differential distribution between SAT and VAT. Our data suggested that methylprednisolone could inhibit Wnt/ß-catenin signaling pathway in SAT and VAT, increase the expression of ATGL and HSL in SAT, and decrease the expression of ATGL and HSL in VAT. The differential expression of lipolysis enzymes induced by methylprednisolone between SAT and VAT might play a crucial role in fat distribution. Those findings would offer novel insights into the mechanisms of GCs induced fat distribution.