目的观察β-catenin/Slug信号特异性抑制剂FH535与EMT的关系,探讨LPCAT1在调节子宫颈癌细胞侵袭、转移和生长中的作用。方法采用sh-NC和sh-LPCAT1转染Hela细胞,利用载体(Vector)组和LPCAT1过表达质粒转染SiHa细胞,将SiHa细胞分为对照组(...目的观察β-catenin/Slug信号特异性抑制剂FH535与EMT的关系,探讨LPCAT1在调节子宫颈癌细胞侵袭、转移和生长中的作用。方法采用sh-NC和sh-LPCAT1转染Hela细胞,利用载体(Vector)组和LPCAT1过表达质粒转染SiHa细胞,将SiHa细胞分为对照组(Con)、LPCAT1组、LPCAT1+FH535组和FH535组。运用CCK-8法和集落形成试验检测子宫颈癌细胞的增殖。通过伤口愈合试验和Transwell实验检测子宫颈癌细胞的转移、侵袭能力。应用Western blot分析细胞中LPCAT1、β-catenin/Slug信号通路和EMT相关蛋白的表达。结果与Vector组相比,LPCAT1组SiHa细胞的活力、集落数、迁移和侵袭细胞数均显著增加(P<0.05);与sh-NC组相比,sh-LPCAT1组Hela细胞的活力、集落数、迁移和侵袭细胞数均显著降低(P<0.05)。与LPCAT1组相比,LPCAT1+FH535组SiHa细胞中Wnt4(1.18±0.05 vs 0.80±0.06)、β-catenin(1.05±0.08 vs 0.77±0.05)、Slug(1.13±0.06 vs 0.28±0.02)、Cyclin D1(0.99±0.06 vs 0.44±0.02)、N-cadherin(0.91±0.07 vs 0.46±0.03)和vimentin(0.95±0.06 vs 0.49±0.03)表达降低(P<0.05),E-cadherin(0.44±0.03 vs 0.58±0.03)表达增加(P<0.05)。此外,与LPCAT1组相比,LPCAT1+FH535组SiHa细胞的集落数(224±15 vs 146±11)、迁移数(85±3 vs 51±4)和侵袭数(166±10 vs 90±5)均降低(P<0.05)。结论LPCAT1表达增加可能通过激活β-catenin/Slug信号通路促进子宫颈癌的转移和进展,LPCAT1的靶向治疗有望提高子宫颈癌患者的预后。展开更多
Breast cancer remains the most prevalent malignancy among women worldwide,with triple-negative breast cancer(TNBC) representing its most aggressive and lethal subtype.TNBC is characterized by high rates of recurrence ...Breast cancer remains the most prevalent malignancy among women worldwide,with triple-negative breast cancer(TNBC) representing its most aggressive and lethal subtype.TNBC is characterized by high rates of recurrence and lung metastasis after surgery,severely impacting patient quality of life.Recent studies highlight the critical role of metabolic reprogramming in driving cancer recurrence,migration,and invasion.While the underlying mechanisms remain complex and not fully elucidated,transcriptomic analyses comparing primary and metastatic breast cancer tissues from TNBC and Luminal patients have identified lysophosphatidylcholine acyltransferase 1(LPCAT1) as a key enzyme upregulated in lung metastases and TNBC.LPCAT1 is strongly associated with poor prognosis due to its activation of the TGFβ signaling pathway.This activation is driven by LPCAT1's ability to increase cellular ATP levels,fostering a high-energy state that stimulates ATPase activity.Consequently,ATP-dependent chromatin remodeling via the BAF complex,which includes double PHD finger 2(DPF2) as a critical subunit,regulates gene transcription essential for tumor progression.Through the LPCAT1-DPF2-TGFBR2 axis,TNBC cells enhance TGFβ signaling,promoting malignant behavior and metastasis.Addressing this,we developed a reduction-responsive nanoparticle platform for the systemic delivery of LPCAT1-targeted si RNA(si LPCAT1),which has shown significant efficacy in suppressing TNBC tumor growth and metastasis.These findings suggest that nanoparticle-mediated si LPCAT1 delivery represents a promising therapeutic strategy for advanced TNBC treatment.展开更多
This study aimed to investigate the relationships between LPCAT1 expression and clinicopathologic parameters of hepatocellular carcinoma(HCC),further,to explore the effect of LPCAT1 on overall survival(OS)in patients ...This study aimed to investigate the relationships between LPCAT1 expression and clinicopathologic parameters of hepatocellular carcinoma(HCC),further,to explore the effect of LPCAT1 on overall survival(OS)in patients with HCC,and its possible mechanism.Bioinformatics analysis using high throughput RNA-sequencing data from TCGA was utilized to explore the differential expression of LPCAT1 between normal and tumor tissues,and the associations between LPCAT1 expression and clinicopathological parameters.Survival analyses and subgroup survival analyses were utilized to elucidate the effect of LPCAT1 on OS in patients with HCC.Univariate analysis and multivariate analysis were used to investigate the prognostic factors.Potential LPCAT1 related tumor genes were identified by the methodology of differentially expressed genes(DEGs)screening.GO term enrichment analysis,KEGG pathway analysis and the PPI network were used to explore the potential mechanism.LPCAT1 was significantly overexpressed in HCC tumor tissues compared with normal tissues.The LPCAT1 expression was related to tumor grade,ECOG score,AFP and TNM stage,with P values of 0.000,0.000,0.007 and 0.000,respectively.Multivariate analysis demonstrated that LPCAT1 expression was independently associated with OS,with an HR of 1.04(CI:1.01–1.06,P=0.003).The KEGG pathway enrichment analyses showed that overlapped DEGs mainly participate in the cell cycle.Finally,we identified a hub gene,CDK1,which has been reported to act on the cell cycle,consistent with the result of KEGG enrichment analysis.Collectively,these data confirmed LPCAT1 was upregulated in HCC,and was an independent predictor of the prognosis.展开更多
Lysophosphatidylcholine acyltransferase 1(LPCAT1)is a phospholipid acyltransferase that promotes phospholipid synthesis and plasma membrane reconstruction.Exosomes play an important role in tumor metastasis.The releas...Lysophosphatidylcholine acyltransferase 1(LPCAT1)is a phospholipid acyltransferase that promotes phospholipid synthesis and plasma membrane reconstruction.Exosomes play an important role in tumor metastasis.The release and uptake of exosomes are key steps of their functions and depend on plasma membrane fusion and plasma membrane receptors,respectively.The purpose of this study was to explore whether LPCAT1-induced plasma membrane remodeling would change the secretion and uptake behavior of exosomes in tumor cells.We first confirmed the abnormally high expression of LPCAT1 in colorectal cancer cells by quantitative real-time PCR(qPCR)and Western blot analysis.Then,SW620 cells were used as exosome source cells,and SW480 cells were used as exosome receiver cells.Exosomes from SW620 cells could effectively promote the migration of SW480 cells.When LPCAT1 expression was reduced via siRNA knockdown in the source cells,the secretion of exosomes was downregulated,thus weakening the pro-migratory effects of exosomes on target cells.Conversely,when LPCAT1 was knocked down in target cells,the uptake of exosomes in target cells also decreased sharply.These results undoubtedly revealed that LPCAT1 is functionally associated with the release and internalization of exosomes in colorectal cancer cells and could affect the paracrine effects of exosomes,preliminarily extending the classical metabolic function of LPCAT1 to exosome-related pathways.展开更多
文摘目的观察β-catenin/Slug信号特异性抑制剂FH535与EMT的关系,探讨LPCAT1在调节子宫颈癌细胞侵袭、转移和生长中的作用。方法采用sh-NC和sh-LPCAT1转染Hela细胞,利用载体(Vector)组和LPCAT1过表达质粒转染SiHa细胞,将SiHa细胞分为对照组(Con)、LPCAT1组、LPCAT1+FH535组和FH535组。运用CCK-8法和集落形成试验检测子宫颈癌细胞的增殖。通过伤口愈合试验和Transwell实验检测子宫颈癌细胞的转移、侵袭能力。应用Western blot分析细胞中LPCAT1、β-catenin/Slug信号通路和EMT相关蛋白的表达。结果与Vector组相比,LPCAT1组SiHa细胞的活力、集落数、迁移和侵袭细胞数均显著增加(P<0.05);与sh-NC组相比,sh-LPCAT1组Hela细胞的活力、集落数、迁移和侵袭细胞数均显著降低(P<0.05)。与LPCAT1组相比,LPCAT1+FH535组SiHa细胞中Wnt4(1.18±0.05 vs 0.80±0.06)、β-catenin(1.05±0.08 vs 0.77±0.05)、Slug(1.13±0.06 vs 0.28±0.02)、Cyclin D1(0.99±0.06 vs 0.44±0.02)、N-cadherin(0.91±0.07 vs 0.46±0.03)和vimentin(0.95±0.06 vs 0.49±0.03)表达降低(P<0.05),E-cadherin(0.44±0.03 vs 0.58±0.03)表达增加(P<0.05)。此外,与LPCAT1组相比,LPCAT1+FH535组SiHa细胞的集落数(224±15 vs 146±11)、迁移数(85±3 vs 51±4)和侵袭数(166±10 vs 90±5)均降低(P<0.05)。结论LPCAT1表达增加可能通过激活β-catenin/Slug信号通路促进子宫颈癌的转移和进展,LPCAT1的靶向治疗有望提高子宫颈癌患者的预后。
基金supported by the National Natural Science Foundation of China (82173392,81874226,82072930 and 81802700)the grants from Guangdong Science and Technology Department (2024B1515040006,2021A1515111106,2020A1515011298,and 2019A1515011932)+6 种基金Guangdong Province Outstanding Youth Fund Project (2021B1515020066)Guangzhou Province Basic Research Fund (202201020576)Guangzhou Science and Technology Bureau (2024A03J0846,20210303004,and 202103000093)the Natural Science Foundation of Hunan Province (2023JJ50149)111 Project (B20056)the “Three million for Three Years” Project of the High-level Talent Special Funding Scheme of Sun Yat-Sen Memorial HospitalYouth Doctor Program Fund of the Second Affiliated Hospital,Army Medical University (2023YQB003)。
文摘Breast cancer remains the most prevalent malignancy among women worldwide,with triple-negative breast cancer(TNBC) representing its most aggressive and lethal subtype.TNBC is characterized by high rates of recurrence and lung metastasis after surgery,severely impacting patient quality of life.Recent studies highlight the critical role of metabolic reprogramming in driving cancer recurrence,migration,and invasion.While the underlying mechanisms remain complex and not fully elucidated,transcriptomic analyses comparing primary and metastatic breast cancer tissues from TNBC and Luminal patients have identified lysophosphatidylcholine acyltransferase 1(LPCAT1) as a key enzyme upregulated in lung metastases and TNBC.LPCAT1 is strongly associated with poor prognosis due to its activation of the TGFβ signaling pathway.This activation is driven by LPCAT1's ability to increase cellular ATP levels,fostering a high-energy state that stimulates ATPase activity.Consequently,ATP-dependent chromatin remodeling via the BAF complex,which includes double PHD finger 2(DPF2) as a critical subunit,regulates gene transcription essential for tumor progression.Through the LPCAT1-DPF2-TGFBR2 axis,TNBC cells enhance TGFβ signaling,promoting malignant behavior and metastasis.Addressing this,we developed a reduction-responsive nanoparticle platform for the systemic delivery of LPCAT1-targeted si RNA(si LPCAT1),which has shown significant efficacy in suppressing TNBC tumor growth and metastasis.These findings suggest that nanoparticle-mediated si LPCAT1 delivery represents a promising therapeutic strategy for advanced TNBC treatment.
基金This study was supported by National Natural Science Foundation of China(No.#81872380)Natural Science Foundation of Chongqing(No.cstc2018jscx-mszdX0039).
文摘This study aimed to investigate the relationships between LPCAT1 expression and clinicopathologic parameters of hepatocellular carcinoma(HCC),further,to explore the effect of LPCAT1 on overall survival(OS)in patients with HCC,and its possible mechanism.Bioinformatics analysis using high throughput RNA-sequencing data from TCGA was utilized to explore the differential expression of LPCAT1 between normal and tumor tissues,and the associations between LPCAT1 expression and clinicopathological parameters.Survival analyses and subgroup survival analyses were utilized to elucidate the effect of LPCAT1 on OS in patients with HCC.Univariate analysis and multivariate analysis were used to investigate the prognostic factors.Potential LPCAT1 related tumor genes were identified by the methodology of differentially expressed genes(DEGs)screening.GO term enrichment analysis,KEGG pathway analysis and the PPI network were used to explore the potential mechanism.LPCAT1 was significantly overexpressed in HCC tumor tissues compared with normal tissues.The LPCAT1 expression was related to tumor grade,ECOG score,AFP and TNM stage,with P values of 0.000,0.000,0.007 and 0.000,respectively.Multivariate analysis demonstrated that LPCAT1 expression was independently associated with OS,with an HR of 1.04(CI:1.01–1.06,P=0.003).The KEGG pathway enrichment analyses showed that overlapped DEGs mainly participate in the cell cycle.Finally,we identified a hub gene,CDK1,which has been reported to act on the cell cycle,consistent with the result of KEGG enrichment analysis.Collectively,these data confirmed LPCAT1 was upregulated in HCC,and was an independent predictor of the prognosis.
文摘Lysophosphatidylcholine acyltransferase 1(LPCAT1)is a phospholipid acyltransferase that promotes phospholipid synthesis and plasma membrane reconstruction.Exosomes play an important role in tumor metastasis.The release and uptake of exosomes are key steps of their functions and depend on plasma membrane fusion and plasma membrane receptors,respectively.The purpose of this study was to explore whether LPCAT1-induced plasma membrane remodeling would change the secretion and uptake behavior of exosomes in tumor cells.We first confirmed the abnormally high expression of LPCAT1 in colorectal cancer cells by quantitative real-time PCR(qPCR)and Western blot analysis.Then,SW620 cells were used as exosome source cells,and SW480 cells were used as exosome receiver cells.Exosomes from SW620 cells could effectively promote the migration of SW480 cells.When LPCAT1 expression was reduced via siRNA knockdown in the source cells,the secretion of exosomes was downregulated,thus weakening the pro-migratory effects of exosomes on target cells.Conversely,when LPCAT1 was knocked down in target cells,the uptake of exosomes in target cells also decreased sharply.These results undoubtedly revealed that LPCAT1 is functionally associated with the release and internalization of exosomes in colorectal cancer cells and could affect the paracrine effects of exosomes,preliminarily extending the classical metabolic function of LPCAT1 to exosome-related pathways.
