Objective·To explore the expression of sorting nexin 1(SNX1)in colorectal cancer(CRC)and its impact on the proliferation and migration of CRC cells.Methods·Transcriptomic data and clinical pathological information of CRC were obtained from The Cancer Genome Atlas(TCGA),Genotype-Tissue Expression(GTEx),and Gene Expression Omnibus(GEO)databases for enrichment analysis with Gene Set Enrichment Analysis(GSEA)software.The expression of SNX1 in CRC tissues and cells was detected by quantitative real-time polymerase chain reaction(qPCR),Western blotting,and immunohistochemistry staining(IHC).Small interfering RNA(siRNA)was used to knock down the expression of SNX1 to observe its effect on tumor cell proliferation and migration.Correlation analysis was conducted to explore the potential molecular mechanisms underlying SNX1-mediated CRC cell migration,and mRNA level validation was performed in SNX1 knockdown cell lines.Results·Analysis of CRC patients data in TCGA and tissue microarrays revealed that SNX1 expression was downregulated in CRC tissues and correlated with tumor diameter and distant metastasis.Knockdown of SNX1 enhanced tumor cell proliferation and migration.The expression of SNX1 was negatively correlated with metastasis associated in colon cancer 1(MACC1),mesenchymal to epithelial transition factor(MET),and Notch;knockdown of SNX1 led to upregulation of these genes.Silencing SNX1 resulted in the downregulation of the epithelial marker cadherin 1(CDH1)and the upregulation of vimentin(VIM)and Snail family transcriptional repressor 1(SNAI1).Conclusion·SNX1 expression was significantly downregulated in CRC tissues and correlated with patient prognosis.Low expression of SNX1 enhanced the proliferation and migration of CRC cells and was associated with the MACC1-MET pathway and EMT.SNX1 may serve as a potential biomarker for poor prognosis and a novel therapeutic target in CRC.

Objective:To investigate the expression of FGD6(FYVE,RhoGEF,and PH domain containing 6)in lung adenocarcinoma(LUAD)tissues and explore its impact on LUAD cells proliferation,apoptosis,migration,invasion,and the possible mechanism.Methods:By searching bioinformatics websites and databases,the differences in the expression of FGD6 gene in LUAD,paracancerous tissues and normal lung tissues were analyzed,and further analyzed the correlation between the expression of FGD6 and the survival prognosis of LUAD patients as well as the correlation with the clinicopathological features of LUAD patients.Two different siRNAs(si-FGD6-1,si-FGD6-2)targeting FGD6 gene were transfected into LUAD cell lines(A549 and NCI-H23)using lipofection.The knockdown efficiency of the siRNAs was detected by real-time fluorescence quantitative PCR and Western blotting.CCK-8 assay,clone formation assay and FCM assay were used to detect the effects of silencing FGD6 expression on the proliferation and apoptosis of A549 and NCI-H23 cells;Wound healing assay assay and Transwell assay were used to detect the effects of silencing FGD6 expression on the migratory and invasive ability of A549 and NCI-H23 cells.Subsequently,Gene Set Enrichment Analysis(GESA)was performed based on the transcriptome data of LUAD patients in The Cancer Genome Atlas(TCGA)database,and it was hypothesized that FGD6 might regulate the Hippo signaling pathway in LUAD cells.Real-time fluorescence quantitative PCR and Western blotting were used to detect the effects of silencing FGD6 expression on the connective tissue growth factor(CTGF)and cysteine-rich 61(CYR61)genes and the phosphorylation of the Hippo signaling pathway downstream in LUAD cells.The effect of the expression level of phosphorylated Yes-associated protein(YAP)in the Hippo signaling pathway.Results:Database analysis showed that FGD6 expression was up-regulated in a variety of tumors,and the expression level in LUAD was significantly higher than that in normal tissues(P<0.001).The overall survival time of patients with high expression of FGD6 was less than that of those with low expression(P<0.05),and it was positively correlated with the clinical stage and lymph node metastatic status of LUAD patients.After knocking down FGD6 expression,the expression levels of FGD6 mRNA and protein in A549 and NCI-H23 cells were significantly down-regulated,and their cell proliferation,anti-apoptosis,migration and invasion abilities were significantly reduced(all P<0.01).The results of real-time fluorescence quantitative PCR showed that knockdown of FGD6 expression led to significant down-regulation of the expression levels of CTGF and CYR61 mRNA,the downstream targeting factors of the Hippo signaling pathway(both P<0.01),while the results of Western blotting showed that the expression levels of phosphorylated Yes-associated protein(p-YAP)were significantly down-regulated in the Hippo signaling pathway(P<0.01).Conclusion:FGD6 is highly expressed in LUAD tissues,and its high expression is associated with poor prognosis.Knockdown of FGD6 gene can inhibit LUAD cells proliferation,apoptosis,migration and invasion,and activate the Hippo pathway,suggesting its potential as a therapeutic target in LUAD.

Objective:To investigate the expression of FGD6(FYVE,RhoGEF,and PH domain containing 6)in lung adenocarcinoma(LUAD)tissues and explore its impact on LUAD cells proliferation,apoptosis,migration,invasion,and the possible mechanism.Methods:By searching bioinformatics websites and databases,the differences in the expression of FGD6 gene in LUAD,paracancerous tissues and normal lung tissues were analyzed,and further analyzed the correlation between the expression of FGD6 and the survival prognosis of LUAD patients as well as the correlation with the clinicopathological features of LUAD patients.Two different siRNAs(si-FGD6-1,si-FGD6-2)targeting FGD6 gene were transfected into LUAD cell lines(A549 and NCI-H23)using lipofection.The knockdown efficiency of the siRNAs was detected by real-time fluorescence quantitative PCR and Western blotting.CCK-8 assay,clone formation assay and FCM assay were used to detect the effects of silencing FGD6 expression on the proliferation and apoptosis of A549 and NCI-H23 cells;Wound healing assay assay and Transwell assay were used to detect the effects of silencing FGD6 expression on the migratory and invasive ability of A549 and NCI-H23 cells.Subsequently,Gene Set Enrichment Analysis(GESA)was performed based on the transcriptome data of LUAD patients in The Cancer Genome Atlas(TCGA)database,and it was hypothesized that FGD6 might regulate the Hippo signaling pathway in LUAD cells.Real-time fluorescence quantitative PCR and Western blotting were used to detect the effects of silencing FGD6 expression on the connective tissue growth factor(CTGF)and cysteine-rich 61(CYR61)genes and the phosphorylation of the Hippo signaling pathway downstream in LUAD cells.The effect of the expression level of phosphorylated Yes-associated protein(YAP)in the Hippo signaling pathway.Results:Database analysis showed that FGD6 expression was up-regulated in a variety of tumors,and the expression level in LUAD was significantly higher than that in normal tissues(P<0.001).The overall survival time of patients with high expression of FGD6 was less than that of those with low expression(P<0.05),and it was positively correlated with the clinical stage and lymph node metastatic status of LUAD patients.After knocking down FGD6 expression,the expression levels of FGD6 mRNA and protein in A549 and NCI-H23 cells were significantly down-regulated,and their cell proliferation,anti-apoptosis,migration and invasion abilities were significantly reduced(all P<0.01).The results of real-time fluorescence quantitative PCR showed that knockdown of FGD6 expression led to significant down-regulation of the expression levels of CTGF and CYR61 mRNA,the downstream targeting factors of the Hippo signaling pathway(both P<0.01),while the results of Western blotting showed that the expression levels of phosphorylated Yes-associated protein(p-YAP)were significantly down-regulated in the Hippo signaling pathway(P<0.01).Conclusion:FGD6 is highly expressed in LUAD tissues,and its high expression is associated with poor prognosis.Knockdown of FGD6 gene can inhibit LUAD cells proliferation,apoptosis,migration and invasion,and activate the Hippo pathway,suggesting its potential as a therapeutic target in LUAD.

Recent studies have discovered a selective autophagy-lipophagy, which can selectively identify and degrade lipids and plays an important role in regulating cellular lipid metabolism and maintaining intracellular lipid homeostasis. The process of lipophagy can be directly or indirectly regulated by genes, enzymes, transcriptional regulators and other factors. This review examines the role of lipophagy in reducing liver lipid content, regulating pancreatic lipid metabolism, and regulating adipose tissue differentiation, and summarizes the findings of the molecules (Rab GTPase, enzymes, ion channels, transcription factors, small molecular substances) involved in the regulation of lipophagy, which points to new directions for the treatment of diseases caused by lipid accumulation.
Adipose Tissue ; Autophagy ; Homeostasis ; Lipid Metabolism ; Liver