LncRNAs play important roles in the regulation of podocyte apoptosis in diabetic nephropathy (DN). However, the role of lncRNA SNHG17 in controlling mitophagy-induced apoptosis of podocytes in DN is unknown. This study aims to elucidate the underlying mechanism of lncRNA SNHG17 in the regulation of mitophagy-induced apoptosis of podocytes in DN. LncRNA SNHG17 and Mammalian Sterile 20-like kinase 1 (Mst1) expression were upregulated in glomeruli and podocytes of DM mice and high glucose-treated podocytes, whereas Parkin expression was downregulated. LncRNA SNHG17 overexpression suppressed mitophagy and induced apoptosis of podocytes while silencing lncRNA SNHG17 promoted mitophagy and reduced the apoptosis of podocytes. In addition, lncRNA SNHG17 interacted with Mst1 and regulated the degradation of Mst1. We further found lncRNA SNHG17 regulated Parkin expression through Mst1. Mechanistically, lncRNA SNHG17 regulated Parkin-dependent mitophagy and apoptosis of podocytes through regulating Mst1. Finally, silencing lncRNA SNHG17 promoted mitophagy and relieved DNin vivo. In conclusion, lncRNA SNHG17 knockdown promotes Parkin-dependent mitophagy and reduces apoptosis of podocytes through regulating the degradation of Mst1.
Forkhead box P3 (FoxP3) expression in papillary thyroid carcinoma (PTC) is associated with resistance to radioiodine treatment. The sodium iodine symporter (NIS) is a plasma membrane glycoprotein, the repression of which may render the tumor refractive to radioiodine therapy. In this study, samples from 90 PTCs as well as 40 normal thyroid tissues were examined for FoxP3 and NIS by immunohistochemistry and real-time PCR. We found that FoxP3 was associated with decreased NIS expression. Lentiviral-mediated FoxP3-overexpressing cells were constructed and real-time PCR and western blotting were performed to evaluate the expression of NIS. Meanwhile, key members of the transforming growth factor-β1 (TGF-β1) pathway were explored by ELISA and immunofluorescence and a neutralizing TGF-β1 antibody was used to block activity. In vitro, FoxP3 overexpression significantly reduced NIS transcript and protein levels and the TGF-β1 pathway was activated. However, treatment with neutralizing TGF-β1 antibody partially abrogated FoxP3-induced NIS repression. These findings suggest that FoxP3 could compromise NIS expression by inducing TGF-β1.
Abstract Background: Folium Artemislae Argyl (FAA) is a traditional Chinese herb medicine widely used in clinic. However, the underlying mechanisms of its anticancer effects have not been fully understood. Methods: In this study, we applied a network pharmacology approach to dig out the potential mechanisms of FAA against breast cancer. Results: We obtained 9 active ingredients and 236 potential targets from FAA in total to construct a network, which showed that quercetin served as the major ingredient in FAA. AKT1 (RAC-alpha serine/threonine-protein kinase), MYC (Myc proto-oncogene protein), CASP3 (Caspase-3), EGFR (Epidermal growth factor receptor), JUN (Transcription factor AP-1), CCND1 (G1/S-specific cyclin-D1), VEGFA (Vascular endothelial growth factor A), ESR1 (Estrogen receptor), MAPK1 (Mitogen-activated protein kinase 1) and EGF (Pro-epidermal growth factor) were identified as key targets of FAA in the treatment of breast cancer. The protein protein interaction (PPI) cluster demonstrated that AKT1 was the seed in this cluster, indicating that AKT1 played a crucial role in connecting other nodes in the PPI network. This enrichment demonstrated that FAA was highly related to signal transduction, endocrine system, replication and repair, cell growth and death. The enrichment results also verified that the underlying mechanisms of FAA against breast cancer might be attributed to coordinated regulation of several cancer-related pathways, such as MAPK signaling pathway, mammalian target of rapamycin (mTOR) signaling pathway, among of others. Conclusions: To summarize, this study aimed to identify the potential targets and pathways of FAA as a treatment against breast cancer using the network pharmacology approach, and systematically elucidate the mechanisms of FAA in the treatment of breast cancer.
Objective To investigate the expression of O6-methylguanine-DNA methytransferase (MGMT) and X-ray repair cross complementing 1 (XRCC1) in breast cancer, and their relationship with clinical prognostic factors. Methods Immunohistochemistry (S-P) was performed for MGMT and XRCC1 on 110 specimens of breast cancer, 19 specimens of fibroadenoma and 11 specimens of normal breast tissues. Results The positive expression rate of MGMT was 71.8%, which had a correlation with pathological classification, pathological grades of infitrating ductal carcinoma ( IDG), axillas lymph nodes metastasis, and expression of ER ( P ＜ 0.05). The positive expression rate of XRCC1 was 30.9%, which had a correlation with the tumor size and the pathological grades of IDG. The expression rate of MGMT had a positive correlation with XRCC1 (P ＜0.05). The survival analysis showed that MGMT and XRCC1 may be considered a independent maker in breast cancer ( P ＜ 0.05 ). Conclusion MGMT and XRCC1 were important pathological signs to evaluate the malignancy degree and prognosis of the breast cancer. These markers play an important role in working out the treatment prescription for breast cancer patients.
Key words:
Breast cancer; Prognosis; Immunohistochemistry
Background. Family history of diabetes (FHD) and lifestyle are associated with type 2 diabetes (T2DM), but little is known about the FHD diet interactions. We aimed to analyze the interactions of FHD and lifestyle factors in Chinese T2DM onset. Methods. This was a cross-sectional survey in central urban China (n = 1234 patients with T2DM and n = 8615 non-T2DM subjects). The biological interactions, defined by Rothman interactions, between FHD and each dietary factor were analyzed by using the synergy index (S) scores. Results. After adjustment for age, gender, BMI, and WHR, a uniparental FHD (OR = 2.84, 95% CI: 2.36-3.42, P < 0.001), a paternal history of FHD (OR = 2.53, 95% CI: 1.91-3.35, P < 0.001), a maternal history of FHD (OR = 3.27, 95% CI: 2.67-4.02, P < 0.001), a biparental history of FHD (OR = 5.26, 95% CI: 2.98-9.31, P < 0.001), and a FHD, irrespective of the parent (OR = 3.59, 95% CI: 3.08-4.17, P < 0.001), were associated with T2DM onset. There were significant interactions between FHD and consuming <15 g/d of potatoes (S = 1.54, 95% CI: 1.12-2.12), <8 g/d of poultry (S = 1.51, 95% CI: 1.04-2.17), <85 g/d of fresh fruits (S = 2.17, 95% CI: 1.63-2.88), and no freshly squeezed juice (S = 2.25, 95% CI: 1.46-3.49). Conclusions. Risk of T2DM was synergistically affected by FHD and dietary habits. Nutrition educational intervention may decrease the prevalence of T2DM in the Chinese with FHD.
Abstract Context Diabetes, hypertension and dyslipidemia accelerates the incidence of cardiovascular disease (CVD) events. However, data regarding the association between main cardiometabolic morbidities such as diabetes, hypertension, and dyslipidemia and the subsequent risk of CVD events in Chinese adults are still limited. Objective To investigate the associations between individual and combined cardiometabolic morbidities and incident cardiovascular events in Chinese adults. Methods Baseline data were obtained from a prospective, nationwide, and population-based cohort study in China during 2011–2012. A total of 133 572 participants aged ≥40 years were included in the study. The main outcome measures were CVD events. Results Compared with participants without diabetes, hypertension and dyslipidemia, participants with only diabetes (hazard ratio [HR], 1.58; 95% CI, 1.32-1.90) or only hypertension (2.04; 1.82-2.28) exhibited significantly higher risk for CVD events, while participants with only dyslipidemia (0.97; 0.84-1.12) exhibited no significantly higher risk for CVD events. When analyzed collectively, participants with diabetes plus hypertension (HR, 2.67; 95% CI, 2.33-3.06), diabetes plus dyslipidemia (1.57; 1.32-1.87), and hypertension plus dyslipidemia (2.12; 1.88-2.39) exhibited significantly higher risk for CVD. Moreover, participants with the combination of diabetes, hypertension, and dyslipidemia exhibited the highest risk for CVD events (HR, 3.06; 95% CI, 2.71-3.46). Multivariable-adjusted HRs (95% CIs) for CVD associated with diabetes based on fasting glucose ≥7.0 mmol/L, oral glucose tolerance test 2-hour glucose ≥11.1 mmol/L, and hemoglobin A1c ≥6.5% were 1.64 (1.51-1.78), 1.57 (1.45-1.69), and 1.54 (1.42-1.66), respectively; associated with hypertension based on systolic blood pressure ≥140 mmHg and diastolic blood pressure ≥90 mmHg were 1.89 (1.76-2.03) and 1.74 (1.60-1.88), respectively; associated with dyslipidemia based on total cholesterol ≥6.22 mmol/L, low-density lipoprotein cholesterol ≥4.14 mmol/L, high-density lipoprotein cholesterol <1.04 mmol/L, and triglycerides ≥2.26 mmol/L were 1.18 (1.08-1.30), 1.30 (1.17-1.44), 1.00 (0.92-1.09), and 1.10 (1.01-1.20), respectively. Conclusion Diabetes, hypertension and dyslipidemia showed additive associations with the risk of CVD events in middle-aged and elderly Chinese adults.
Aerobic glycolysis is a hallmark of tumor cells. SGLT1 plays a vital role in glucose metabolism. However, whether SGLT1 could promote cell growth and proliferation in breast cancer remains unclear. Here, we investigated the expression of SGLT1 in breast cancer and examined its role in malignant behavior and prognosis. Further, we examined the SGLT1 expression in breast cancer tissues and its relationship with clinicopathologic characteristics. We clarified that SGLT1 was overexpressed in HER2+ breast cancer cell lines and was affected by HER2 status. We further found that SGLT1 affected breast cancer cell proliferation and patient survival by mediating cell survival pathway activation. SGLT1 was overexpressed in HER2+ breast cancers and associated with lymph node metastasis and HER2+ status. Inhibition of HER2 decreased SGLT1 expression, and the extracellular acidification rate was also reduced in the UACC812 and SKBR3 cell lines. These changes could be reversed by proteasome inhibitor treatment. Knockdown of SGLT1 blocked PI3K/Akt/mTOR signaling, thereby inhibiting cell proliferation. Further, we demonstrated that high SGLT1 was significantly correlated with shorter survival in all breast cancer patients and specifically in HER2+ breast cancer patients. Therefore, we conclude that SGLT1 is overexpressed in HER2+ breast cancer, thereby promoting cell proliferation and shortening survival by activating PI3K/Akt/mTOR signaling. This study submits that SGLT1 is promising not only as a novel biomarker of HER2+ breast cancer subtype but also as a potential drug target.
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