Mesenchymal stem cell-derived exosomes block malignant behaviors of hepatocellular carcinoma stem cells through a lncRNA C5orf66-AS1/microRNA-127-3p/DUSP1/ERK axis

Yan, Chao; Wan, Huaibin; Wu, Lin; Liu, Junjie; Zhu, Zhiqiang; Gao, Dazhi

doi:10.1007/s13577-021-00599-9

Cited by 31 publications

(17 citation statements)

References 43 publications

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“…Furthermore, by using exosome inhibitor GW4869, it was disclosed that exosomes were necessary for the regulation of HCC progression by HCC-MSCs, which, to the best of our knowledge, had not been reported by other studies. However, several published studies display that exosomes from bone marrow MSCs impede the progression of HCC ( 25 , 37 , 38 ). The differences between the current study and those previous ones are because MSCs from different sources have different roles in cancer progression, in which CA-MSCs promote cancer progression while bone marrow MSCs exert the reverse effect.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Exosomes From Cancer-Associated Mesenchymal Stem Cells Transmit TMBIM6 to Promote the Malignant Behavior of Hepatocellular Carcinoma via Activating PI3K/AKT Pathway

Shang

Liu

et al. 2022

Front. Oncol.

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ObjectiveCancer-associated mesenchymal stem cells (MSCs) regulate the progression of cancers through exosome-delivered components, while few studies are conducted on hepatocellular carcinoma (HCC). This study aimed to evaluate the effect of exosomes from HCC-associated MSCs (HCC-MSCs) on HCC cellular functions and the potential regulatory mechanism.MethodsHCC cells (Huh7 and PLC) were cultured normally or co-cultured with HCC-MSCs, HCC-MSCs plus GW4869, or HCC-MSC-derived exosomes; then mRNA sequencing and RT-qPCR validation were conducted. Subsequently, candidate genes were sorted out and modified in HCC cells. Next, TMBIM6-modified HCC-MSCs were used to treat HCC cells.ResultsBoth HCC-MSCs and their derived exosomes promoted proliferation, invasion, sphere formation ability but suppressed apoptosis in HCC cells (all p < 0.05); however, the effect of HCC-MSCs on these cellular functions was repressed by exosome inhibitor (GW4869). Subsequently, TMBIM6, EEF2, and PRDX1 were sorted out by mRNA sequencing and RT-qPCR validation as candidate genes implicated in the regulation of HCC cellular functions by HCC-MSC-derived exosomes. Among them, TMBIM6 had a potent effect (all p < 0.05), while EEF2 and PRDX1 had less effect on regulating HCC cell viability and invasion. Next, direct silencing TMBIM6 repressed viability, sphere formation, invasion, epithelial–mesenchymal transition (EMT), and PI3K/AKT pathway but promoted apoptosis in HCC cells; however, overexpressing TMBIM6 showed the opposite effect. Furthermore, incubating with exosomes from TMBIM6-modified HCC-MSCs presented a similar effect as direct TMBIM6 modification in HCC cells.ConclusionHCC-MSC-derived exosomes transmit TMBIM6 to promote malignant behavior via PI3K/AKT pathway in HCC.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Exosomes From Cancer-Associated Mesenchymal Stem Cells Transmit TMBIM6 to Promote the Malignant Behavior of Hepatocellular Carcinoma via Activating PI3K/AKT Pathway

Shang

Liu

et al. 2022

Front. Oncol.

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“…Furthermore, MSCs have been shown to suppress cancer by inhibiting tumor angiogenesis through endothelial cells apoptosis and capillary degeneration [ 80 ]. Recently, Gu and colleagues reported that MSCs‑derived Exo were able to block hepatocellular CSCs malignancy via a lncRNA C5orf66‑AS1/ microRNA‑127‑3p/dual-specificity phosphatase 1 (DUSP1)/ERK axis [ 81 ]. Considering that Exo are involved in both oncogenic and tumor-suppressing roles of MSCs, they treated hepatocellular CSCs with MSC-Exo, and found that the proliferation, migration, invasion, angiogenesis-stimulating and self-renewal abilities of CSCs were significantly decreased through lncRNA C5orf66‑AS1/microRNA‑127‑3p/DUSP1 axis and inhibiting the phosphorylation of ERK in vitro.…”

Section: Mscs In Cancer Progressionmentioning

confidence: 99%

Mesenchymal stem cells in cancer progression and anticancer therapeutic resistance

et al. 2021

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Increasing evidence indicates that the tumor microenvironment appears to play an increasingly important role in cancer progression and therapeutic resistance. Several types of cells within the tumor stroma had distinct impacts on cancer progression, either promoting or inhibiting cancer cell growth. Mesenchymal stem cells (MSCs) are a distinct type of cells that is linked to tumor development. MSCs are recognized for homing to tumor locations and promoting or inhibiting cancer cell proliferation, angiogenesis and metastasis. Moreover, emerging studies suggests that MSCs are also involved in therapeutic resistance. In this review, we analyzed the existing researches and elaborate on the functions of MSCs in cancer progression and anticancer therapeutic resistance, demonstrating that MSCs may be a viable cancer therapeutic target.

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“…Pathways and GO annotation include signal transduction [ [108], SOCS1 [109], GPR183 [110], AKR1B10 [111], TREM2 [112], SCD (stearoyl-CoA desaturase) [113], GCK (glucokinase) [114], LPL (lipoprotein lipase) [115], ANGPTL8 [116], UGT1A1 [117], IL2RA [118], CDKN1A [119], GAS6 [120], ACE2 [121], NLRP6 [122], S1PR4 [123], FADS2 [124], FASN (fatty acid synthase) [125], TIMP3 [126], CHI3L1 [127], ADAMTSL2 [128], FNDC5 [129], MMP9 [130] and TMC4 [131] were involved in progression of NAFLD. EGR1 [132], NR4A2 [133], DUSP1 [134], DLK1 [135], SIK1 [136], CCN1 [137], CEBPD (CCAAT enhancer binding protein delta) [138], SOCS2 [139], IRS2 [91], GADD45B [140], CXCL2 [141], ZFAND5 [142], EGR3 [143], PTGS2 [144], KL (klotho) [145], SOCS3 [146], MMP1 [147], CXCR4 [148], THBS1 [149], SLC7A11 [150], FAM83A [151], EGR2 [152], ZFP36 [153], NR0B2 [154], CCN2…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of differentially expressed genes in non alcoholic fatty liver disease using next generation sequencing data

Vastrad¹

2021

Preprint

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Non alcoholic fatty liver disease (NAFLD) is the most common metabolic disease in humans, affecting the majority of individuals. In the current investigation, we aim to identify potential key genes linked with NAFLD through bioinformatics analyses of next generation sequencing (NGS) dataset. NGS dataset of GSE135251 from the Gene Expression Omnibus (GEO) database were retrieved. Differentially expressed genes (DEGs) were obtained by DESeq2 package. g:Profiler database was further used to identify the potential gene ontology (GO) and REACTOME pathways. Protein-protein interaction (PPI) network was constructed using the Hippie interactome database. miRNet and NetworkAnalyst databases were used to establish a miRNA-hub gene regulatory network and TF-hub gene regulatory network for the hub genes. Hub genes were verified based on receiver operating characteristic curve (ROC) analysis. Totally, 951 DEGs were identified including 476 up regulated genes and 475 down regulated genes screened in NAFLD and normal control. GO showed that DEGs were significantly enhanced for signaling and regulation of biological quality. REACTOME pathway analysis revealed that DEGs were enriched in signaling by interleukins and extracellular matrix organization. ESR2, JUN, PTN, PTGER3, CEBPB, IKBKG, HSPA8, SFN, CDKN1A and E2F1 were indicated as hub genes from PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network. Furthermore, ROC analysis revealed that ESR2, JUN, PTN, PTGER3, CEBPB, IKBKG, HSPA8, SFN, CDKN1A and E2F1 might serve as diagnostic biomarkers in NAFLD. The current investigation provided insights into the molecular mechanism of NAFLD that might be useful in further investigations.

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Mesenchymal stem cell-derived exosomes block malignant behaviors of hepatocellular carcinoma stem cells through a lncRNA C5orf66-AS1/microRNA-127-3p/DUSP1/ERK axis

Cited by 31 publications

References 43 publications

RETRACTED: Exosomes From Cancer-Associated Mesenchymal Stem Cells Transmit TMBIM6 to Promote the Malignant Behavior of Hepatocellular Carcinoma via Activating PI3K/AKT Pathway

RETRACTED: Exosomes From Cancer-Associated Mesenchymal Stem Cells Transmit TMBIM6 to Promote the Malignant Behavior of Hepatocellular Carcinoma via Activating PI3K/AKT Pathway

Mesenchymal stem cells in cancer progression and anticancer therapeutic resistance

Bioinformatics analysis of differentially expressed genes in non alcoholic fatty liver disease using next generation sequencing data

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