Objective To analyze the relationship between malignant transformation and abnormal expression of eukaryotic initiation factor 3 （eIF3 p36） in human bronchial epithelial （16HBE） cells induced by cadmium chloride ...Objective To analyze the relationship between malignant transformation and abnormal expression of eukaryotic initiation factor 3 （eIF3 p36） in human bronchial epithelial （16HBE） cells induced by cadmium chloride （CdCl2）. Methods 16HBE cells were treated several times with different concentrations of CdCl2. Tumorigenic potential of transformed cells was identified by assays for anchorage-independent growth in soft agar and for tumorigenicity in nude mice after the 35th passage. Total RNA was isolated from 16HBE cells induced by CdC12, including non-transformed, Cd-transformed, and Cd-tumorigenic cell lines. Special primers for eIF3 p36 were designed and the expression of eIF3 mRNA in different cell lines was detected with fluorescent quantitative-polymerase chain reaction technique （FQ-PCR）. Results The 35th passage of 16HBE cells transformed by CdCl2 exhibited overlapping growth. Compared with the non-transformed cells, colonies of transformed cell lines in soft agar showed statistically significant increases and dose-dependent effects （P〈0.01）. All Cd-induced transformed cell lines formed rumors in nude mice within 2 weeks of inoculation, but none of the mice injected with non-transformed cells showed tumors even after 3 weeks. All tumors were pathologically identified as poorly differentiated squamous cell carcinoma. The eIF3 p36 genes in different stages of 16HBE cells transformed by CdCl2 were elevated as compared with the non-transformed control （P〈0.01）, and the eIF3 expression increased with the degree of cell malignancy. Conclusion CdCl2 is capable of inducing morphological transformation in 16HBE cells and transformed cells are potentially tumorigenic. Over-expression of eIF3 p36 is positively correlated with malignant transformation of 16HBE cells induced by CdCl2 and may be one of the molecular mechanisms potentially responsible for carcinogenesis due to Cd.展开更多
Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expr...Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and recurrence.Nevertheless,the efficacy of FAK phosphorylation inhibitors is currently limited.Thus,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis.This study examined the correlation between FAK expression and the prognosis of HCC.Additionally,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor model.The expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying mechanisms.The results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in vivo.Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited.Consequently,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.展开更多
Hepatocellular carcinoma is prone to invasion and metastasis.It often receives a low diagnosis rate in the early stage but has an extremely high mortality rate.Epithelial-mesenchymal transformation(EMT)is a key factor...Hepatocellular carcinoma is prone to invasion and metastasis.It often receives a low diagnosis rate in the early stage but has an extremely high mortality rate.Epithelial-mesenchymal transformation(EMT)is a key factor in promoting tumor cell invasion and metastasis.Circular RNA(circRNA)is involved in regulating EMT in hepatocarcinoma cells through multiple pathways,thereby affecting the occurrence and progression of hepatocellular carcinoma.This article mainly reviews the research progress of circRNA related to EMT core transcription factors,circRNA that promotes EMT in liver cancer,and circRNA that inhibits EMT in liver cancer.展开更多
Posterior capsule opacification(PCO),the most common complication after cataract surgery,is caused by the proliferation,migration and epithelial-mesenchymal transition(EMT)of residual lens epithelial cells in the caps...Posterior capsule opacification(PCO),the most common complication after cataract surgery,is caused by the proliferation,migration and epithelial-mesenchymal transition(EMT)of residual lens epithelial cells in the capsule bag.Although the surface modification and drug loading of intraocular lens(IOLs)have been effective in preventing PCO to some extent,the intraocular safety of anti-proliferative drug application is still a major limitation in clinical application.In this study,we used non-viral gene delivery systems in combination with layer-by-layer(LBL)self-assembly technology,and the modified IOL could effectively prevent the development of PCO by interfering with the EMT process mediated by the platelet-derived growth factor receptor-α(PDGFR-α).Herein,the gene fragments were wrapped by electrostatic conjugation using polyethyleneimine-graft-poly(ethylene glycol)to form gene complexes.Gene complexes were characterized by dynamic light scattering,transmission electron microscopy(TEM)and agarose gel electrophoresis,and evaluated for storage and serum stability.The layer assembly behavior of the IOL surface,changes in optical properties and the release behavior of the gene complexes were characterized using quartz crystal microbalance,UV-vis,contact angle and TEM.In vitro experiments showed that the IOL coating has good bio-compatibility and can achieve the corresponding transfection effect,and the released gene complexes exhibited excellent cell internalization and lysosomal escape behaviors,as well as effective inhibition of PDGFR-αexpression and its mediated EMT process.The early PCO prevention effect and bio-compatibility evaluation of the modified IOL in vivo were evaluated by implantation into animal eyes.This study provides a new strategy for the development of surface modifications of small nucleic acid drugs and non-toxic EMT interference therapies for PCO.展开更多
Objective To study the alterations of FHIT gene and P16 gene in malignant transformed human bronchial epithelial cells induced by crystalline nickel sulfide using an immortal human bronchial epithelial cell line, and ...Objective To study the alterations of FHIT gene and P16 gene in malignant transformed human bronchial epithelial cells induced by crystalline nickel sulfide using an immortal human bronchial epithelial cell line, and to explore the molecular mechanism of nickel carcinogenesis. Methods 16HBE cells were treated 6 times with different concentrations of NiS in vitro, and the degree of malignant transformation was determined by assaying the anchorage-independent growth and tumorigenicity. Malignant transformed cells and tumorigenic cells were examined for alterations of FHIT gene and P16 gene using RT-PCR, DNA sequencing, silver staining PCR-SSCP and Western blotting. Results NiS-treated cells exhibited overlapping growth. Compared wkh that of negative control cells, soft agar colony formation efficiency of NiS-treated cells showed significant increases （P〈0.01） and dose-dependent effects. NiS-treated cells could form tumors in nude mice, and a squamous cell carcinoma was confirmed by histopathological examination. No mutation of exon 2 and exons 2-3, no abnormal expression in pl6 gene and mutation of FHIT exons 5-8 and exons 1-4 or exons 5-9 were observed in transformed cells and tumorigenic cells. However, aberrant transcripts or loss of expression of the FHIT gene and Fhit protein was observed in transformed cells and tumorigenic cells. One of the aberrant transcripts in the FHIT gene was confirmed to have a deletion of exon 6, exon 7, exon 8, and an insertion of a 36 bp sequence replacing exon 6-8. Conclusions The FHIT gene rather than the P16 gene, plays a definite role in nickel carcinogenesis. Alterations of the FHIT gene induced by crystalline NiS may be a molecular event associated with carcinogen, chromosome fragile site instability and cell malignant transformation. FHIT may be an important target gene activated by nickel and other exotic carcinogens.展开更多
目的探讨Eph A2基因表达沉默对胃癌AGS细胞上皮-间质转化的影响机制。方法将对数生长期的胃癌AGS细胞接种于6孔板并分为Eph A2 si RNA组、阴性对照组和空白对照组。采用Eph A2 si RNA转染胃癌AGS细胞,采用实时定量聚合酶链反应检测转染...目的探讨Eph A2基因表达沉默对胃癌AGS细胞上皮-间质转化的影响机制。方法将对数生长期的胃癌AGS细胞接种于6孔板并分为Eph A2 si RNA组、阴性对照组和空白对照组。采用Eph A2 si RNA转染胃癌AGS细胞,采用实时定量聚合酶链反应检测转染细胞Eph A2的表达,采用相差显微镜观察细胞形态的变化,采用Transwell实验检测转染细胞的侵袭能力,应用蛋白质印迹法检测转染细胞E-cadherin和vimentin蛋白的表达。结果 Eph A2 si RNA组的Eph A2 m RNA相对表达量(0.343±0.035)明显低于阴性对照组(0.950±0.036)和空白对照组(0.997±0.065),差异均有统计学意义(P<0.05);Eph A2 si RNA组胃癌AGS细胞呈上皮细胞样,阴性对照组和空白对照组细胞呈间质样细胞;Eph A2si RNA组的侵袭细胞数[(29.1±2.6)个]明显少于阴性对照组[(52.2±2.6)个]和空白对照组[(56.2±4.0)个],差异均有统计学意义(P<0.05);Eph A2 si RNA组E-cadherin蛋白的表达量较阴性对照组和空白对照的E-cadherin蛋白的表达量明显上调,而vimentin蛋白的表达量明显下调,差异均有统计学意义(P<0.05)。结论沉默AGS细胞Eph A2的表达能够抑制胃癌细胞由上皮样细胞向间质样细胞转化,降低AGS细胞的侵袭力,上调上皮性标志物E-cadherin的表达,下调间质性标志物vimentin的表达。展开更多
Background and Aims:Hepatocellular carcinoma(HCC)is among the most common malignant tumors globally.Circular RNAs(circRNAs),as a type of noncoding RNAs,reportedly participate in various tumor biological processes.Howe...Background and Aims:Hepatocellular carcinoma(HCC)is among the most common malignant tumors globally.Circular RNAs(circRNAs),as a type of noncoding RNAs,reportedly participate in various tumor biological processes.However,the role of circHDAC1_004 in HCC remains unclear.Thus,we aimed to explore the role and the underlying mechanisms of circHDAC1_004 in the development and progression of HCC.Methods:Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect circHDAC1_004 expression(circ_0005339)in HCC.Sanger sequencing and agarose gel electrophoresis were used to determine the structure of circHDAC1_004.In vitro and in vivo experiments were used to determine the biological function of circHDAC1_004 in HCC.Herein,qRT-PCR,RNA immunoprecipitation,western blotting,and a luciferase reporter assay were used to explore the relationships among circHDAC1_004,miR-361-3p,and NACC1.Results:circHDAC1_004 was upregulated in HCC and significantly associated with poor overall survival.circHDAC1_004 promoted HCC cell proliferation,stemness,migration,and invasion.In addition,circHDAC1_004 upregulated human umbilical vein endothelial cells(HUVECs)and promoted angiogenesis through exosomes.circHDAC1_004 promoted NACC1 expression and stimulated the epithelialmesenchymal transition pathway by sponging miR-361-3p.Conclusions:We found that circHDAC1_004 overexpression enhanced the proliferation,stemness,and metastasis of HCC via the miR-361-3p/NACC1 axis and promoted HCC angiogenesis through exosomes.Our findings may help develop a possible therapeutic strategy for HCC.展开更多
BACKGROUND Colorectal cancer(CRC) is a common malignant tumor. Alcohol consumption is positively correlated with CRC malignant metastasis;however, the mechanism is unclear. The interaction between laminin-γ2(LAMC2) a...BACKGROUND Colorectal cancer(CRC) is a common malignant tumor. Alcohol consumption is positively correlated with CRC malignant metastasis;however, the mechanism is unclear. The interaction between laminin-γ2(LAMC2) and integrin-β1(ITGB1) plays a role in premetastatic niche signaling, which may induce epithelial mesenchymal transformation(EMT) and lead to metastasis.AIM To investigate the effects of alcohol on CRC metastasis from the molecular mechanism of the premetastatic niche.METHODS The interaction between LAMC2 and ITGB1 was measured by Duolink assay, and the expression levels of LAMC2, ITGB1 and focal adhesion kinase(FAK), snail, fibronectin, N-cadherin and special AT-rich sequence binding protein 1(SATB1) were measured by quantitative real-time polymerase chain reaction, immunohistochemistry and western blotting. Interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α) and IL-6 levels were measured via enzyme-linked immunosorbent assay, histopathological assessment via hematoxylin eosin staining, and determination of aberrant crypt foci via methylene blue.RESULTS The lymph node metastasis rate was higher in the alcohol group than non-alcohol group. There was a significant increase in interaction signals between LAMC2 and ITGB1, and an increase in phosphorylate-FAK/FAK, snail, fibronectin, N-cadherin and SATB1, whereas E-cadherin was reduced in the alcohol group compared to the non-alcohol group in both animal and clinical samples. Serum IL-1β, TNF-α and IL-6 were higher in alcohol group than in non-alcohol group. Alcohol may promote CRC metastasis by influencing the molecular mechanism of the premetastatic niche.CONCLUSION Our study suggests that alcohol promotes EMT-mediated premetastatic niche formation of CRC by activating the early interaction between LAMC2 and ITGB1 and lead to CRC metastasis.展开更多
基金the National Natural Science Foundation of China (No. 30371195)Guangdong NaturalScience Foundation (No. 06022672)+1 种基金Guangzhou Science and Technology Foundation (No. 2003Z2-E0191/E0192)Guangzhou Municipal Department of Education (No. 1002)
文摘Objective To analyze the relationship between malignant transformation and abnormal expression of eukaryotic initiation factor 3 （eIF3 p36） in human bronchial epithelial （16HBE） cells induced by cadmium chloride （CdCl2）. Methods 16HBE cells were treated several times with different concentrations of CdCl2. Tumorigenic potential of transformed cells was identified by assays for anchorage-independent growth in soft agar and for tumorigenicity in nude mice after the 35th passage. Total RNA was isolated from 16HBE cells induced by CdC12, including non-transformed, Cd-transformed, and Cd-tumorigenic cell lines. Special primers for eIF3 p36 were designed and the expression of eIF3 mRNA in different cell lines was detected with fluorescent quantitative-polymerase chain reaction technique （FQ-PCR）. Results The 35th passage of 16HBE cells transformed by CdCl2 exhibited overlapping growth. Compared with the non-transformed cells, colonies of transformed cell lines in soft agar showed statistically significant increases and dose-dependent effects （P〈0.01）. All Cd-induced transformed cell lines formed rumors in nude mice within 2 weeks of inoculation, but none of the mice injected with non-transformed cells showed tumors even after 3 weeks. All tumors were pathologically identified as poorly differentiated squamous cell carcinoma. The eIF3 p36 genes in different stages of 16HBE cells transformed by CdCl2 were elevated as compared with the non-transformed control （P〈0.01）, and the eIF3 expression increased with the degree of cell malignancy. Conclusion CdCl2 is capable of inducing morphological transformation in 16HBE cells and transformed cells are potentially tumorigenic. Over-expression of eIF3 p36 is positively correlated with malignant transformation of 16HBE cells induced by CdCl2 and may be one of the molecular mechanisms potentially responsible for carcinogenesis due to Cd.
基金supported by the National Natural Science Foundation of China Fund Project(82272956).
文摘Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and recurrence.Nevertheless,the efficacy of FAK phosphorylation inhibitors is currently limited.Thus,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis.This study examined the correlation between FAK expression and the prognosis of HCC.Additionally,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor model.The expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying mechanisms.The results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in vivo.Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited.Consequently,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.
基金Medical Research Project of Xi’an Science and Technology Bureau(Project No.22YXYJ0134)。
文摘Hepatocellular carcinoma is prone to invasion and metastasis.It often receives a low diagnosis rate in the early stage but has an extremely high mortality rate.Epithelial-mesenchymal transformation(EMT)is a key factor in promoting tumor cell invasion and metastasis.Circular RNA(circRNA)is involved in regulating EMT in hepatocarcinoma cells through multiple pathways,thereby affecting the occurrence and progression of hepatocellular carcinoma.This article mainly reviews the research progress of circRNA related to EMT core transcription factors,circRNA that promotes EMT in liver cancer,and circRNA that inhibits EMT in liver cancer.
基金supported by the Zhejiang Provincial Natural Science Foundation(LR23H180001)the Key Scientific and Technological Innovation Projects in Wenzhou(ZY2021002)+1 种基金Medical&Health Technology Program of Zhejiang Province(2022RC051)the Zhejiang Science and Technology Program of Traditional Chinese Medicine(2022ZB220).
文摘Posterior capsule opacification(PCO),the most common complication after cataract surgery,is caused by the proliferation,migration and epithelial-mesenchymal transition(EMT)of residual lens epithelial cells in the capsule bag.Although the surface modification and drug loading of intraocular lens(IOLs)have been effective in preventing PCO to some extent,the intraocular safety of anti-proliferative drug application is still a major limitation in clinical application.In this study,we used non-viral gene delivery systems in combination with layer-by-layer(LBL)self-assembly technology,and the modified IOL could effectively prevent the development of PCO by interfering with the EMT process mediated by the platelet-derived growth factor receptor-α(PDGFR-α).Herein,the gene fragments were wrapped by electrostatic conjugation using polyethyleneimine-graft-poly(ethylene glycol)to form gene complexes.Gene complexes were characterized by dynamic light scattering,transmission electron microscopy(TEM)and agarose gel electrophoresis,and evaluated for storage and serum stability.The layer assembly behavior of the IOL surface,changes in optical properties and the release behavior of the gene complexes were characterized using quartz crystal microbalance,UV-vis,contact angle and TEM.In vitro experiments showed that the IOL coating has good bio-compatibility and can achieve the corresponding transfection effect,and the released gene complexes exhibited excellent cell internalization and lysosomal escape behaviors,as well as effective inhibition of PDGFR-αexpression and its mediated EMT process.The early PCO prevention effect and bio-compatibility evaluation of the modified IOL in vivo were evaluated by implantation into animal eyes.This study provides a new strategy for the development of surface modifications of small nucleic acid drugs and non-toxic EMT interference therapies for PCO.
基金This work was supported by a grant (No. 39170651 and 30200235) from National Natural Science Foundation of China.
文摘Objective To study the alterations of FHIT gene and P16 gene in malignant transformed human bronchial epithelial cells induced by crystalline nickel sulfide using an immortal human bronchial epithelial cell line, and to explore the molecular mechanism of nickel carcinogenesis. Methods 16HBE cells were treated 6 times with different concentrations of NiS in vitro, and the degree of malignant transformation was determined by assaying the anchorage-independent growth and tumorigenicity. Malignant transformed cells and tumorigenic cells were examined for alterations of FHIT gene and P16 gene using RT-PCR, DNA sequencing, silver staining PCR-SSCP and Western blotting. Results NiS-treated cells exhibited overlapping growth. Compared wkh that of negative control cells, soft agar colony formation efficiency of NiS-treated cells showed significant increases （P〈0.01） and dose-dependent effects. NiS-treated cells could form tumors in nude mice, and a squamous cell carcinoma was confirmed by histopathological examination. No mutation of exon 2 and exons 2-3, no abnormal expression in pl6 gene and mutation of FHIT exons 5-8 and exons 1-4 or exons 5-9 were observed in transformed cells and tumorigenic cells. However, aberrant transcripts or loss of expression of the FHIT gene and Fhit protein was observed in transformed cells and tumorigenic cells. One of the aberrant transcripts in the FHIT gene was confirmed to have a deletion of exon 6, exon 7, exon 8, and an insertion of a 36 bp sequence replacing exon 6-8. Conclusions The FHIT gene rather than the P16 gene, plays a definite role in nickel carcinogenesis. Alterations of the FHIT gene induced by crystalline NiS may be a molecular event associated with carcinogen, chromosome fragile site instability and cell malignant transformation. FHIT may be an important target gene activated by nickel and other exotic carcinogens.
文摘目的探讨Eph A2基因表达沉默对胃癌AGS细胞上皮-间质转化的影响机制。方法将对数生长期的胃癌AGS细胞接种于6孔板并分为Eph A2 si RNA组、阴性对照组和空白对照组。采用Eph A2 si RNA转染胃癌AGS细胞,采用实时定量聚合酶链反应检测转染细胞Eph A2的表达,采用相差显微镜观察细胞形态的变化,采用Transwell实验检测转染细胞的侵袭能力,应用蛋白质印迹法检测转染细胞E-cadherin和vimentin蛋白的表达。结果 Eph A2 si RNA组的Eph A2 m RNA相对表达量(0.343±0.035)明显低于阴性对照组(0.950±0.036)和空白对照组(0.997±0.065),差异均有统计学意义(P<0.05);Eph A2 si RNA组胃癌AGS细胞呈上皮细胞样,阴性对照组和空白对照组细胞呈间质样细胞;Eph A2si RNA组的侵袭细胞数[(29.1±2.6)个]明显少于阴性对照组[(52.2±2.6)个]和空白对照组[(56.2±4.0)个],差异均有统计学意义(P<0.05);Eph A2 si RNA组E-cadherin蛋白的表达量较阴性对照组和空白对照的E-cadherin蛋白的表达量明显上调,而vimentin蛋白的表达量明显下调,差异均有统计学意义(P<0.05)。结论沉默AGS细胞Eph A2的表达能够抑制胃癌细胞由上皮样细胞向间质样细胞转化,降低AGS细胞的侵袭力,上调上皮性标志物E-cadherin的表达,下调间质性标志物vimentin的表达。
基金supported by the National Natural Science Foundation of China(grant number 81871260)The training programe of“Double hundred”young and middle-aged medical and health talents in Wuxi(grant number BJ020034)Health Research Projects of Wuxi Health Committee(grant number M202106)。
文摘Background and Aims:Hepatocellular carcinoma(HCC)is among the most common malignant tumors globally.Circular RNAs(circRNAs),as a type of noncoding RNAs,reportedly participate in various tumor biological processes.However,the role of circHDAC1_004 in HCC remains unclear.Thus,we aimed to explore the role and the underlying mechanisms of circHDAC1_004 in the development and progression of HCC.Methods:Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect circHDAC1_004 expression(circ_0005339)in HCC.Sanger sequencing and agarose gel electrophoresis were used to determine the structure of circHDAC1_004.In vitro and in vivo experiments were used to determine the biological function of circHDAC1_004 in HCC.Herein,qRT-PCR,RNA immunoprecipitation,western blotting,and a luciferase reporter assay were used to explore the relationships among circHDAC1_004,miR-361-3p,and NACC1.Results:circHDAC1_004 was upregulated in HCC and significantly associated with poor overall survival.circHDAC1_004 promoted HCC cell proliferation,stemness,migration,and invasion.In addition,circHDAC1_004 upregulated human umbilical vein endothelial cells(HUVECs)and promoted angiogenesis through exosomes.circHDAC1_004 promoted NACC1 expression and stimulated the epithelialmesenchymal transition pathway by sponging miR-361-3p.Conclusions:We found that circHDAC1_004 overexpression enhanced the proliferation,stemness,and metastasis of HCC via the miR-361-3p/NACC1 axis and promoted HCC angiogenesis through exosomes.Our findings may help develop a possible therapeutic strategy for HCC.
基金Supported by the National Natural Science Foundation of China,No.81673944
文摘BACKGROUND Colorectal cancer(CRC) is a common malignant tumor. Alcohol consumption is positively correlated with CRC malignant metastasis;however, the mechanism is unclear. The interaction between laminin-γ2(LAMC2) and integrin-β1(ITGB1) plays a role in premetastatic niche signaling, which may induce epithelial mesenchymal transformation(EMT) and lead to metastasis.AIM To investigate the effects of alcohol on CRC metastasis from the molecular mechanism of the premetastatic niche.METHODS The interaction between LAMC2 and ITGB1 was measured by Duolink assay, and the expression levels of LAMC2, ITGB1 and focal adhesion kinase(FAK), snail, fibronectin, N-cadherin and special AT-rich sequence binding protein 1(SATB1) were measured by quantitative real-time polymerase chain reaction, immunohistochemistry and western blotting. Interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α) and IL-6 levels were measured via enzyme-linked immunosorbent assay, histopathological assessment via hematoxylin eosin staining, and determination of aberrant crypt foci via methylene blue.RESULTS The lymph node metastasis rate was higher in the alcohol group than non-alcohol group. There was a significant increase in interaction signals between LAMC2 and ITGB1, and an increase in phosphorylate-FAK/FAK, snail, fibronectin, N-cadherin and SATB1, whereas E-cadherin was reduced in the alcohol group compared to the non-alcohol group in both animal and clinical samples. Serum IL-1β, TNF-α and IL-6 were higher in alcohol group than in non-alcohol group. Alcohol may promote CRC metastasis by influencing the molecular mechanism of the premetastatic niche.CONCLUSION Our study suggests that alcohol promotes EMT-mediated premetastatic niche formation of CRC by activating the early interaction between LAMC2 and ITGB1 and lead to CRC metastasis.
