scholarly journals ALCAP2 inhibits lung adenocarcinoma cell proliferation, migration and invasion via the ubiquitination of β-catenin by upregulating the E3 ligase NEDD4L

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Weijie Zhang ◽  
Ruochen Zhang ◽  
Yuanyuan Zeng ◽  
Yue Li ◽  
Yikun Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Nuclear Translocation ◽  
E3 Ligase ◽  
Migration And Invasion ◽  
Drug Candidate ◽  
Proliferation And Metastasis

AbstractLung cancer is recognized as the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) being the predominant subtype, accounting for approximately 85% of lung cancer cases. Although great efforts have been made to treat lung cancer, no proven method has been found thus far. Considering β, β-dimethyl-acryl-alkannin (ALCAP2), a natural small-molecule compound isolated from the root of Lithospermum erythrorhizon. We found that lung adenocarcinoma (LUAD) cell proliferation and metastasis can be significantly inhibited after treatment with ALCAP2 in vitro, as it can induce cell apoptosis and arrest the cell cycle. ALCAP2 also significantly suppressed the volume of tumours in mice without inducing obvious toxicity in vivo. Mechanistically, we revealed that ALCAP2-treated cells can suppress the nuclear translocation of β-catenin by upregulating the E3 ligase NEDD4L, facilitating the binding of ubiquitin to β-catenin and eventually affecting the wnt-triggered transcription of genes such as survivin, cyclin D1, and MMP9. As a result, our findings suggest that targeting the oncogene β-catenin with ALCAP2 can inhibit the proliferation and metastasis of LUAD cells, and therefore, ALCAP2 may be a new drug candidate for use in LUAD therapeutics.

scholarly journals ESCO2 promotes lung adenocarcinoma progression by regulating hnRNPA1 acetylation

2020 ◽  
Author(s):  
Hui-er Zhu ◽  
Tao Li ◽  
Shengnan Shi ◽  
De-xiong Chen ◽  
Weiping Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Nuclear Translocation ◽  
Lactate Production ◽  
Gene Set Enrichment Analysis ◽  
Metabolic Reprogramming ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion

Abstract Background: Emerging evidence indicates that metabolism reprogramming and abnormal acetylation modification play an important role in lung adenocarcinoma (LUAD) progression, although the mechanism is largely unknown. Methods: Here, we used three public databases (Oncomine, Gene Expression Omnibus [GEO], The Cancer Genome Atlas [TCGA]) to analyze ESCO2 (establishment of cohesion 1 homolog 2) expression in LUAD. The biological function of ESCO2 was studied using cell proliferation, colony formation, cell migration, and invasion assays in vitro, and mouse xenograft models in vivo. ESCO2 interacting proteins were searched using gene set enrichment analysis (GSEA) and mass spectrometry. Pyruvate kinase M1/2 (PKM) mRNA splicing assay was performed using RT-PCR together with restriction digestion. LUAD cell metabolism was studied using glucose uptake assays and lactate production. ESCO2 expression was significantly upregulated in LUAD tissues, and higher ESCO2 expression indicated worse prognosis for patients with LUAD. Results: We found that ESCO2 promoted LUAD cell proliferation and metastasis metabolic reprogramming in vitro and in vivo. Mechanistically, ESCO2 increased hnRNPA1 (heterogeneous nuclear ribonucleoprotein A1) binding to the intronic sequences flanking exon 9 (EI9) of PKM mRNA by inhibiting hnRNPA1 nuclear translocation, eventually inhibiting PKM1 isoform formation and inducing PKM2 isoform formation. Conclusions: Our findings confirm that ESCO2 is a key factor in promoting LUAD malignant progression and suggest that it is a new target for treating LUAD.

scholarly journals ESCO2 promotes lung adenocarcinoma progression by regulating hnRNPA1 acetylation

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Hui-er Zhu ◽  
Tao Li ◽  
Shengnan Shi ◽  
De-xiong Chen ◽  
Weiping Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Nuclear Translocation ◽  
Lactate Production ◽  
Gene Set Enrichment Analysis ◽  
Metabolic Reprogramming ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion

Abstract Background Emerging evidence indicates that metabolism reprogramming and abnormal acetylation modification play an important role in lung adenocarcinoma (LUAD) progression, although the mechanism is largely unknown. Methods Here, we used three public databases (Oncomine, Gene Expression Omnibus [GEO], The Cancer Genome Atlas [TCGA]) to analyze ESCO2 (establishment of cohesion 1 homolog 2) expression in LUAD. The biological function of ESCO2 was studiedusing cell proliferation, colony formation, cell migration, and invasion assays in vitro, and mouse xenograft models in vivo. ESCO2 interacting proteins were searched using gene set enrichment analysis (GSEA) and mass spectrometry. Pyruvate kinase M1/2 (PKM) mRNA splicing assay was performed using RT-PCR together with restriction digestion. LUAD cell metabolism was studied using glucose uptake assays and lactate production. ESCO2 expression was significantly upregulated in LUAD tissues, and higher ESCO2 expression indicated worse prognosis for patients with LUAD. Results We found that ESCO2 promoted LUAD cell proliferation and metastasis metabolic reprogramming in vitro and in vivo. Mechanistically, ESCO2 increased hnRNPA1 (heterogeneous nuclear ribonucleoprotein A1) binding to the intronic sequences flanking exon 9 (EI9) of PKM mRNA by inhibiting hnRNPA1 nuclear translocation, eventually inhibiting PKM1 isoform formation and inducing PKM2 isoform formation. Conclusions Our findings confirm that ESCO2 is a key factor in promoting LUAD malignant progression and suggest that it is a new target for treating LUAD.

scholarly journals C1GALT1, Negatively Regulated by miR-181d-5p, Promotes Tumor Progression via Upregulating RAC1 in Lung Adenocarcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaoxia Dong ◽  
Yongyu Liu ◽  
Xinzhou Deng ◽  
Jun Shao ◽  
Shuangyue Tian ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Bioinformatic Analysis ◽  
Tumor Formation ◽  
Negative Regulator ◽  
Migration And Invasion ◽  
Loss Of Function

Glycosyltransferases are frequently dysregulated in lung cancer. Core 1 β 1, 3-galactosyltransferase 1 (C1GALT1), an enzyme highly expressed in various cancers, is correlated with tumor initiation and development. However, the role of C1GALT1 in lung cancer remains poorly understood. In this study, through bioinformatic analysis and clinical validation, we first discovered that C1GALT1 expression was upregulated in lung adenocarcinoma (LUAD) tissues and was closely related to poor prognosis in patients with LUAD. Gain- and loss-of-function experiments showed that C1GALT1 promoted LUAD cell proliferation, migration, and invasion in vitro, as well as tumor formation in vivo. Further investigation demonstrated that RAC1 expression was positively regulated by C1GALT1 in LUAD, whereas silencing Rac1 could reverse C1GALT1-induced tumor growth and metastasis. Moreover, miR-181d-5p was identified as a negative regulator for C1GALT1 in LUAD. As expected, the inhibitory effects of miR-181d-5p on LUAD cell proliferation, migration, and invasion were counteracted by restoration of C1GALT1. In summary, our results highlight the importance of the miR-181d-5p/C1GALT1/RAC1 regulatory axis during LUAD progression. Thus, C1GALT1 may serve as a potential therapeutic target for LUAD.

scholarly journals ESCO2 promotes lung adenocarcinoma progression by regulating hnRNPA1 acetylation

2021 ◽  
Author(s):  
Hui-er Zhu ◽  
Tao Li ◽  
Shengnan Shi ◽  
De-xiong Chen ◽  
Weiping Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Nuclear Translocation ◽  
Lactate Production ◽  
Gene Set Enrichment Analysis ◽  
Metabolic Reprogramming ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion

Abstract Background: Emerging evidence indicates that metabolism reprogramming and abnormal acetylation modification play an important role in lung adenocarcinoma (LUAD) progression, although the mechanism is largely unknown. Methods: Here, we used three public databases (Oncomine, Gene Expression Omnibus [GEO], The Cancer Genome Atlas [TCGA]) to analyze ESCO2 (establishment of cohesion 1 homolog 2) expression in LUAD. The biological function of ESCO2 was studiedusing cell proliferation, colony formation, cell migration, and invasion assays in vitro, and mouse xenograft models in vivo. ESCO2 interacting proteins were searched using gene set enrichment analysis (GSEA) and mass spectrometry. Pyruvate kinase M1/2 (PKM) mRNA splicing assay was performed using RT-PCR together with restriction digestion. LUAD cell metabolism was studied using glucose uptake assays and lactate production. ESCO2 expression was significantly upregulated in LUAD tissues, and higher ESCO2 expression indicated worse prognosis for patients with LUAD. Results: We found that ESCO2 promoted LUAD cell proliferation and metastasis metabolic reprogramming in vitro and in vivo. Mechanistically, ESCO2 increased hnRNPA1 (heterogeneous nuclear ribonucleoprotein A1) binding to the intronic sequences flanking exon 9 (EI9) of PKM mRNA by inhibiting hnRNPA1 nuclear translocation, eventually inhibiting PKM1 isoform formation and inducing PKM2 isoform formation. Conclusions: Our findings confirm that ESCO2 is a key factor in promoting LUAD malignant progression and suggest that it is a new target for treating LUAD.

scholarly journals Diaphanous related formin 3 knockdown suppresses cell proliferation and metastasis of osteosarcoma cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zehua Zhang ◽  
Fei Dai ◽  
Fei Luo ◽  
Wenjie Wu ◽  
Shuai Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Therapy ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Proliferation And Metastasis ◽  
New Biomarkers

AbstractOsteosarcoma is a malignant osteoblastic tumor that can gravely endanger the lives and health of children and adolescents. Therefore, there is an urgent need to explore new biomarkers for osteosarcoma and determine new targeted therapies to improve the efficacy of osteosarcoma treatment. Diaphanous related formin 3 (DIAPH3) promotes tumorigenesis in hepatocellular carcinoma and lung adenocarcinoma, suggesting that DIAPH3 may be a target for tumor therapy. To date, there have been no reports on the function of DIAPH3 in osteosarcoma. DIAPH3 protein expression in osteosarcoma tissues and healthy bone tissues adjacent to cancer cells was examined by immunohistochemical staining. DIAPH3 mRNA expression correlates with overall survival and reduced disease-free survival. DIAPH3 protein is upregulated in osteosarcoma tissues, and its expression is significantly associated with tumor size, tumor stage, node metastasis, and distant metastasis. Functional in vitro experiments revealed that DIAPH3 knockdown suppressed cell proliferation and suppressed cell migration and invasion of osteosarcoma cell lines MG-63 and HOS. Functional experiments demonstrated that DIAPH3 knockdown inhibited subcutaneous tumor growth and lung metastasis in vivo. In conclusion, DIAPH3 expression can predict the clinical outcome of osteosarcoma. In addition, DIAPH3 is involved in the proliferation and metastasis of osteosarcoma, and as such, DIAPH3 may be a potential therapeutic target for osteosarcoma.

Amplified LncRNA PVT1 promotes lung cancer proliferation and metastasis by facilitating VEGFC expression

2020 ◽  
Vol 98 (6) ◽  
pp. 676-682
Author(s):  
Yanming Pan ◽  
Lantao Liu ◽  
Yongxia Cheng ◽  
Jianbo Yu ◽  
Yukuan Feng
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Tumor Model ◽  
Cancer Proliferation ◽  
Survival Prognosis ◽  
Proliferation And Metastasis ◽  
Factor C ◽  
The Impact

Although the abundance of long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) in lung cancer has been well researched, the underlying mechanisms behind its effects were unknown. Here we investigated the molecular events regulating PVT1 in lung cancer. The pro-proliferative property of PVT1 was examined using a xenograft tumor model. Transwell chambers were used to analyze the impact of PVT1 expression on cell invasiveness and migration. In vivo metastasis was examined by tail-vein-injection in mice. Direct binding of miR-128 to PVT1 was investigated using a probe pulldown assay. The relative expression levels of miR-128 and PVT1 were quantified by real-time polymerase chain reaction and Western blotting. We show here that when PVT1 is amplified, there is a poor survival prognosis for patients with lung cancer. Elevated levels of PVT1 promoted lung cancer cell proliferation and metastasis, both in vitro and in vivo. Mechanistically, we found that PVT1 competes endogenously with miR-128 in the regulation of vascular endothelial growth factor C (VEGFC) expression, which is significantly associated with an unfavorable prognosis in lung cancer. We identified that copy number amplification significantly contributes to the high level of PVT1 transcripts in lung cancer, which promotes cell proliferation and metastatic behavior via modulating VEGFC expression by endogenous competition with miR-128.

scholarly journals MUC3A Promotes Non-Small Cell Lung Cancer Progress via Activating NFκB Pathway and Attenuates Radiosensitivity

2020 ◽  
Author(s):  
Yingming Sun ◽  
Xiaoge Sun ◽  
Chengcheng You ◽  
Shijing Ma ◽  
Yuan Luo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Clinical Outcomes ◽  
Nuclear Translocation ◽  
Xenograft Model ◽  
High Expression ◽  
G1 Arrest ◽  
Nfκb Pathway

Abstract Background: MUC3A is highly expressed in lung adenocarcinoma, but its functions and effects on clinical outcomes are not well understood.Methods: Tissue microarray was used to analysis the relathionship between MUC3A and clinicalpathological charcristics of lung adenocarcinoma; Colony formation and MTT array ware used to detect cell proliferation; WB applied to investigate the protein amount; Transwell was applied to evaluate cell invasion; IF was used to observe the location and expression of targeted proteins; IP was use to prove the binding of proteins. Mcherry-GFP-LC3 II adenovirus and TEM were performed to observe cell autophagy. Xnograft mouse model were used to investigate the effect of MUC3A in vivo.Result: 92 patients’ tumor samples indicated that high expression of MUC3A was associated with poor prognosis, advanced staging, and low differentiation. Co-immunoprecipitation results revealed that MUC3A interacted with RELA. MUC3A activated the NFκB pathway via promoting RELA phosphorylation and interfering the binding of RELA to IκB. MUC3A knockdown significantly suppressed cell proliferation and induced G1 arrest. MUC3A deficiency increased radiation-induced DNA double strain breaks via impairing the BRCA-1/RAD51 pathway and nuclear translocation of P53 and XCRR6. Moreover, MUC3A deficiency induced autophagy in lung cancer cells. MUC3A knockdown significantly suppressed tumor growth in xenograft model and had a synergistic effect with radiation. Less nuclear translocation of RELA and P53 was also observed in tumor tissue in vivo.Conclusion: MUC3A was a potential oncogene, and its high expression was associated with unfavorable clinical outcomes. Patient with high expression of MUC3A should be more frequent follow-up and might benefit less from radiotherapy.

Hsa_circ_0003288 facilitates tumor progression by targeting miR-145 in non–small cell lung cancer cells

2021 ◽  
pp. 1-9
Author(s):  
Li-Na Pan ◽  
Yun-Fang Ma ◽  
Jia-An Hu ◽  
Zhi-Hong Xu
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung

Circular RNA (circRNA) has been shown to participate in various tumors, including lung cancer. In the present study, we explored the expression and functional relevance of hsa_circ_0003288 in human non-small cell lung cancer (NSCLC). We verified that hsa_circ_0003288 expression was upregulated in lung cancer tissues and cell lines. Overexpression of hsa_circ_0003288 dramatically promoted lung cancer cell proliferation, colony formation, inhibited apoptosis, and increased cell migration and invasion in vitro. Xenograft experiments showed that hsa_circ_0003288 overexpression accelerated tumor growth in vivo. Mechanistically, hsa_circ_0003288 negatively regulated miR-145 to exert the oncogenic role in lung cancer. Overexpression of miR-145 decreased cell proliferation, induced apoptosis, and suppressed migration and invasion in lung cancer. Additionally, miR-145 co-transfection abolished the oncogenic role of hsa_circ_0003288. Collectively, these findings identified a novel regulatory role of hsa_circ_0003288/miR-145 axis in the progression of NSCLC.

scholarly journals LncRNA LINC00337 sponges mir-1285-3p to promote proliferation and metastasis of lung adenocarcinoma cells by upregulating YTHDF1

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ru-nan Zhang ◽  
Dong-mei Wu ◽  
Li-ping Wu ◽  
Guo-wei Gao
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gear Up ◽  
Underlying Mechanisms

Abstract Background Emerging studies have shown that long noncoding RNAs (lncRNAs) predominantly function in the carcinogenesis of multiple developing human tumors. The current study aimed to investigate the underlying mechanisms of LINC00337 in lung adenocarcinoma. Methods We analyzed TCGA and GTEx datasets and chose LINC00337 as the research object. Cell proliferation, cell apoptosis, cell cycle, migration, and invasion were detected in the gain and loss experiments of LINC00337 both in vitro and in vivo. Moreover, RNA pull-down, luciferase reporter assays, western blotting analysis, and rescue experiments were performed to investigate the underlying molecular mechanisms of LINC00337 function. Results LINC00337 expression was remarkably upregulated in lung adenocarcinoma. In addition, LINC00337 knockdown was shown to repress cell migration, invasion, and proliferation, as well as the cell cycle, and gear up apoptosis in lung adenocarcinoma in vitro and in vivo. With respect to the mechanism, LINC00337 knockdown boosted miR-1285-3p expression and then restrained YTHDF1 expression post-transcriptionally. Crucially, both miR-1285-3p decrement and YTHDF1 overexpression successfully reversed the influence on cell proliferation, migration, invasion, and apoptosis caused by LINC00337 shRNA. Conclusions These results suggest that LINC00337 acts as an oncogenic lncRNA, targeting miR-1285-3p and regulating YTHDF1 expression, to promote the progression of lung adenocarcinoma.

scholarly journals Anticancer Properties of Carnosol: A Summary of In Vitro and In Vivo Evidence

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 961
Author(s):  
Eric J. O’Neill ◽  
Danja J. Den Hartogh ◽  
Karim Azizi ◽  
Evangelia Tsiani
Keyword(s):  
Cell Proliferation ◽  
Nuclear Translocation ◽  
B Cell Lymphoma ◽  
Migration And Invasion ◽  
Anticancer Properties ◽  
Anticancer Effects ◽  
Cell Proliferation Inhibition ◽  
Apoptotic Marker

Cancer is characterized by unrestricted cell proliferation, inhibition of apoptosis, enhanced invasion and migration, and deregulation of signalling cascades. These properties lead to uncontrolled growth, enhanced survival, and the formation of tumours. Carnosol, a naturally occurring phyto-polyphenol (diterpene) found in rosemary, has been studied for its extensive antioxidant, anti-inflammatory, and anticancer effects. In cancer cells, carnosol has been demonstrated to inhibit cell proliferation and survival, reduce migration and invasion, and significantly enhance apoptosis. These anticancer effects of carnosol are mediated by the inhibition of several signalling molecules including extracellular signal-regulated kinase (ERK), p38, c-Jun N-terminal kinase (JNK), Akt, mechanistic target of rapamycin (mTOR) and cyclooxygenase-2 (COX-2). Additionally, carnosol prevents the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and promotes apoptosis, as indicated by increased levels of cleaved caspase-3, -8, -9, increased levels of the pro-apoptotic marker Bcl-2-associated X (BAX), and reduced levels of the anti-apoptotic marker B-cell lymphoma 2 (Bcl-2). The current review summarizes the existing in vitro and in vivo evidence examining the anticancer effects of carnosol across various tissues.

Sign in / Sign up

Export Citation Format

Share Document