SLC12A5 interacts and enhances SOX18 activity to promote bladder urothelial carcinoma progression via upregulating MMP7

Solute carrier family 12 member 5 (SLC12A5) has an oncogenic role in bladder urothelial carcinoma. The present study aimed to characterize the molecular mechanisms of SLC12A5 in bladder urothelial carcinoma pathogenesis. Functional assays identified that in bladder urothelial carcinoma SLC12A5 interacts with and stabilizes SOX18, and then upregulates matrix metalloproteinase 7 (MMP7). In vivo and in vitro assays were performed to confirm the effect of SLC12A5’s interaction with SOX18 on MMP7‐mediated bladder urothelial carcinoma progression. SLC12A5 was upregulated in human bladder tumors, and correlated with the poor survival of patients with bladder urothelial carcinoma tumor invasion and metastasis, promoted by SLC12A5 overexpression. We demonstrated that SLC12A5 interacted with SOX18, and then upregulated MMP7, thus enhancing tumor progression. Importantly, SLC12A5 expression correlated positively with SOX18 and MMP7 expression in bladder urothelial carcinoma. Furthermore, SLC12A5 expression was suppressed by miR‐133a‐3p. Ectopic expression of SLC12A5 partly abolished miR‐133a‐3p‐mediated suppression of cell migration. SLC12A5‐SOX18 complex‐mediated upregulation on MMP7 was important in bladder urothelial carcinoma progression. The miR‐133a‐3p/SLC12A5/SOX18/MMP7 signaling axis was critical for progression, and provided an effective therapeutic approach against bladder urothelial carcinoma.     

miR-30c Impedes Glioblastoma Cell Proliferation and Migration by Targeting SOX9

miR-30c has been acknowledged as a tumor suppressor in various human cancers, such as ovarian cancer, gastric cancer, and prostate cancer. However, the role of miR-30c in glioblastoma (GBM) needs to be investigated. In our study, we found that the expression of miR-30c was significantly downregulated in GBM tissues and cell lines. We found that overexpression of miR-30c inhibited cellular proliferation of GBM cells in vitro and in vivo. More GBM cells were arrested in the G₀ phase after miR-30c overexpression. Moreover, we showed that miR-30c overexpression suppressed the migration and invasion of GBM cells. Mechanistically, we found that SOX9 was a direct target of miR-30c in GBM cells. Overexpression of miR-30c inhibited the mRNA and protein levels of SOX9 in GBM cells. Moreover, there was a negative correlation between the expression of miR-30c and SOX9 in GBM tissues. Finally, we showed that restoration of SOX9 in GBM cells reversed the proliferation, migration, and invasion of GBM cells transfected with miR-30c mimic. Collectively, our results demonstrated that miR-30c suppressed the proliferation, migration, and invasion of GBM cells via targeting SOX9.     

肺鳞癌治疗新靶点FGFR的研究进展

肺癌是目前全球发病率和死亡率均居前列的恶性肿瘤，其中肺鳞癌经手术、放化疗等综合治疗后，其疗效仍不满意。随着分子靶向治疗在肺腺癌中取得了令人瞩目的成果，而肺鳞癌患者中EGFR基因突变及ALK融合基因少见，急需探索新的靶点指导肺鳞癌患者的临床治疗。研究表明，FGFR家族（FGFR1-4）是肺鳞癌中突变频率较高的基因，FGFR基因的激活突变和扩增与肺鳞癌的发生和发展密切相关，同时许多小分子 FGFR 抑制剂在临床应用中已经取得较好的治疗效果。目前，许多FGFR抑制剂治疗肺鳞癌的临床试验也正在进行研究，针对FGFR靶点的基因治疗可为肺鳞癌的治疗提供一种新的策略。本文就FGFR在肺鳞癌的靶向治疗中的最新研究进展进行综述。     

Differential Expression of PD-L1 Between Sporadic and VHL-Associated Hereditary Clear-Cell Renal Cell Carcinoma and Its Correlation With Clinicopathological Features

Background

Programmed death ligand-1 (PD-L1) is a potential predictive biomarker for immunotherapy in several malignancies. However, the expression level and clinical significance of PD-L1 in von Hippel–Lindau (VHL)-associated hereditary clear-cell renal cell carcinoma (ccRCC) remain unclear.

Acsl4在浸润性乳腺癌组织中的表达及其临床意义

目的:探讨Acsl4在浸润性乳腺癌组织中的表达及其临床意义。方法:采用免疫组织化学法检测108例浸润性乳腺癌组织中Acsl4的表达。结果:108例浸润性乳腺癌组织中,33例(30.6%)阳性表达,75例(69.4%)阴性表达。组织学G3级的乳腺癌组织中Acsl4阳性率为42.3%(22/52),高于G1+G2级的阳性率(19.6%,11/56),差异具有统计学意义(P<0.05)。ER阳性组织的Acsl4的阳性率15.8%(6/38),低于ER阴性的病例(38.6%,27/70),差异具有统计学意义(P<0.05)。Acsl4的表达与患者年龄、肿瘤大小、淋巴结是否转移、HER2、PR、p53、Ki67的表达情况无统计学意义的相关性(P均>0.05)。结论:Acsl4在浸润性乳腺癌组织中存在异常表达,其阳性表达与乳腺癌患者组织学分级较高及ER阴性表达密切相关。     

The Relationship Between Air Pollution and Lung Cancer in Nonsmokers in Taiwan

Introduction

For never-smokers (smoked <100 lifetime cigarettes), lung cancer (LC) has emerged as an important issue. We aimed to investigate the effects of prevalence changes in tobacco smoking and particulate matter (PM) 2.5 (PM_2.5) levels on LC in Taiwan, in relation to contrasting PM_2.5 levels, between Northern Taiwan (NT) and Southern Taiwan (ST).

基于VOSviewer的2019新型冠状病毒病中医临床诊疗可视化分析＊

目的 通过对公开发表在网络和数据库的有关中医药治疗2019新型冠状病毒肺炎（corona virus disease 2019，COVID-19）的文献进行方、药、证的可视化分析，客观全面的对COVID-19的中医药治疗进行探讨，为现代中医临床诊疗提供参考。方法 本文选用运用文献计量学方法和VOSviewer可视化软件对纳入文献中的用药情况进行数据拆分、整理和分析。结果 本研究高质量数据的主要期刊来源是核心期刊《中医杂志》；新冠临床用方以解表清热剂、开窍补益剂、辟秽祛湿剂为主；临床用药以解表药、清热解毒药、化湿祛痰药以及补益药为主；临床治病思路以六经辨证、三焦辨证和卫气营血辨证理论为指导；临床常见证型为湿、热、寒、毒相关证型；重视新冠前期预防以及后期恢复调养；治疗过程用药考究，注重养阴与祛邪并进。结论 新冠的中医临床诊治考病全面，并注重养阴与祛邪并进，可为官方制定治疗方案提供参考。     

竹叶石膏汤合清气化痰丸加减治疗急性加重期慢性阻塞性肺疾病分析

目的:分析竹叶石膏汤合清气化痰丸加减治疗急性加重期慢性阻塞性肺疾病(Acute Exacerbations of Chronic Obstructive Pulmonary Disease,AECOPD)疗效。方法:以2017年1月-2019年1月收治的AECOPD患者80例,随机分为两组,各40例。对照组采用常规西药治疗,观察组在对照组基础上采用竹叶石膏汤合清气化痰丸加减治疗。比较两组治疗前后肺功能指标[第1秒用力呼气容积占预计值百分比(Forced Expiratory Volume,FEV1%)、第一秒用力呼气肺容积(Forced Expiratory Volume,FEV1)]、改良版英国医学研究委员会呼吸问卷(mMRC)、慢阻肺患者自我评估测试问卷(CAT)等评分变化以及疗效。结果:在FEV1%、FEV1等肺功能指标上,两组治疗前对比无统计学差异(P>0.05);而观察组治疗后均高于对照组,二者差异存在统计学意义(P<0.05)。在mMRC、CAT等评分上,两组治疗前差异对比无统计学意义(P>0.05);而观察组治疗后均低于对照组,二者差异存在统计学意义(P<0.05)。在治疗有效率上,对照组总体为82.5%(33/40),观察组总体为95.0%(38/40),二者差异对比存在统计学意义(P<0.05)。结论:竹叶石膏汤合清气化痰丸加减治疗AECOPD的疗效确切,即可有效改善患者肺功能和临床症状,且利于其预后康复,因此值得应用推广。     

新型冠状病毒肺炎中医病因与辨治的思考

新型冠状病毒肺炎是感受新型冠状病毒所致,属于中医学“疫病”的范畴,其病因为吴又可提出的“异气”,与六淫不同,具有生物学属性;侵袭人体主要造成气阴损伤,气化失常,湿饮停聚;治疗当以“逐邪为第一要义”,恢复机体平衡状态。     

The FABP12/PPARγ pathway promotes metastatic transformation by inducing epithelial‐to‐mesenchymal transition and lipid‐derived energy production in prostate cancer cells

Early stage localized prostate cancer (PCa) has an excellent prognosis; however, patient survival drops dramatically when PCa metastasizes. The molecular mechanisms underlying PCa metastasis are complex and remain unclear. Here, we examine the role of a new member of the fatty acid‐binding protein (FABP) family, FABP12, in PCa progression. FABP12 is preferentially amplified and/or overexpressed in metastatic compared to primary tumors from both PCa patients and xenograft animal models. We show that FABP12 concurrently triggers metastatic phenotypes (induced epithelial‐to‐mesenchymal transition (EMT) leading to increased cell motility and invasion) and lipid bioenergetics (increased fatty acid uptake and accumulation, increased ATP production from fatty acid β‐oxidation) in PCa cells, supporting increased reliance on fatty acids for energy production. Mechanistically, we show that FABP12 is a driver of PPARγ activation which, in turn, regulates FABP12''s role in lipid metabolism and PCa progression. Our results point to a novel role for a FABP‐PPAR pathway in promoting PCa metastasis through induction of EMT and lipid bioenergetics.

Abbreviations

AR

androgen receptor

ATP

adenosine triphosphate

CN

copy number

CPT1

carnitine palmitoyltransferase I

CS

citrate synthase

EMT

epithelial–mesenchymal transition

ET

electron transfer‐state

FABP

fatty acid‐binding protein

LD

lipid droplet

OA

oleic acid

PCa

prostate cancer

PPAR

peroxisome proliferator‐activated receptor

PPRE

peroxisome proliferator‐activated receptor response element

TZD

thiazolidinediones