scholarly journals Bmi1 Promotes Cholangiocarcinoma Progression And Correlates With Antitumor Immunity In An Exosome-Dependent Manner

2022 ◽  
Author(s):  
Zengli Liu ◽  
Chunxiao Hu ◽  
Lijie Zheng ◽  
Jialiang Liu ◽  
Kangshuai Li ◽  
...  
Keyword(s):  
Prognostic Biomarker ◽  
Malignant Tumors ◽  
Prognostic Significance ◽  
Clinical Importance ◽  
Immune Checkpoint Blockade ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Intrinsic Immunity ◽  
Bmi1 Expression

Abstract Background: Cholangiocarcinoma (CCA) is a class of malignant tumors originating from bile duct epithelial cells. Due to difficult early diagnosis and limited treatment, the prognosis of CCA is extremely poor. Bmi1 is dysregulated in many human malignancies. However, the prognostic significance and oncogenic role of Bmi1 in cholangiocarcinoma (CCA) are not well elucidated. Methods: In the present study, we investigated its clinical importance and the potential mechanisms in the progression of CCA. We detected Bmi1 expression in a large CCA cohort. We demonstrated Bmi1 was substantially upregulated in CCA tissues and was identified as an independent prognostic biomarker of CCA. Moreover, overexpression of Bmi1 promoted CCA proliferation, migration, and invasion. And, Bmi1 knockdown could inhibit proliferation and metastases of CCA in vitro and in vitro/vivo validation. Interestingly, we found that CCA-derived exosomes contain Bmi1 proteins, which can transfer Bmi1 between CCA cells. The unique Bmi1-containing exosomes promote CCA proliferation and metastasis through autocrine/paracrine mechanisms. In addition, we demonstrated that Bmi1 inhibits CD8+T cell-recruiting chemokines by promoting repressive H2A ubiquitination in CCA cells. Conclusions: Bmi1 is an unfavorable prognostic biomarker of CCA. Our data demonstrate a novel function of Bmi1 in CCA tumorigenesis and metastasis mediated by exosomes. Besides, Bmi1 inhibition may augment immune checkpoint blockade to inhibit tumor progression by activating cell-intrinsic immunity of CCA

scholarly journals Influence of icariin on inflammation, apoptosis, invasion, and tumor immunity in cervical cancer by reducing the TLR4/MyD88/NF-κB and Wnt/β-catenin pathways

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chunyang Li ◽  
Shuangqing Yang ◽  
Huaqing Ma ◽  
Mengjia Ruan ◽  
Luyan Fang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Underlying Mechanism ◽  
Tissue Growth ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Siha Cells ◽  
Cervical Cancer Cells

Abstract Background Cervical cancer is a type of the most common gynecology tumor in women of the whole world. Accumulating data have shown that icariin (ICA), a natural compound, has anti-cancer activity in different cancers, including cervical cancer. The study aimed to reveal the antitumor effects and the possible underlying mechanism of ICA in U14 tumor-bearing mice and SiHa cells. Methods The antitumor effects of ICA were investigated in vivo and in vitro. The expression of TLR4/MyD88/NF-κB and Wnt/β-catenin signaling pathways were evaluated. Results We found that ICA significantly suppressed tumor tissue growth and SiHa cells viability in a dose-dependent manner. Also, ICA enhanced the anti-tumor humoral immunity in vivo. Moreover, ICA significantly improved the composition of the microbiota in mice models. Additionally, the results clarified that ICA significantly inhibited the migration, invasion capacity, and expression levels of TGF-β1, TNF-α, IL-6, IL-17A, IL-10 in SiHa cells. Meanwhile, ICA was revealed to promote the apoptosis of cervical cancer cells by down-regulating Ki67, survivin, Bcl-2, c-Myc, and up-regulating P16, P53, Bax levels in vivo and in vitro. For the part of mechanism exploration, we showed that ICA inhibits the inflammation, proliferation, migration, and invasion, as well as promotes apoptosis and immunity in cervical cancer through impairment of TLR4/MyD88/NF-κB and Wnt/β-catenin pathways. Conclusions Taken together, ICA could be a potential supplementary agent for cervical cancer treatment.

scholarly journals Antimetastatic Effects of Sesamin on Human Head and Neck Squamous Cell Carcinoma through Regulation of Matrix Metalloproteinase-2

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2248 ◽  
Author(s):  
Jian-Ming Chen ◽  
Pei-Yin Chen ◽  
Chia-Chieh Lin ◽  
Ming-Chang Hsieh ◽  
Jen-Tsun Lin
Keyword(s):  
Oral Cancer ◽  
Matrix Metalloproteinase ◽  
Head And Neck ◽  
Mapk Pathway ◽  
Human Head ◽  
Mapk Signaling ◽  
Matrix Metalloproteinase 2 ◽  
Migration And Invasion ◽  
Dependent Manner

Background: Sesamin is a lignin present in sesame oil from the bark of Zanthoxylum spp. Sesamin reportedly has anticarcinogenic potential and exerts anti-inflammatory effects on several tumors. Hypothesis/Purpose: However, the effect of sesamin on metastatic progression in human head and neck squamous carcinoma (HNSCC) remains unknown in vitro and in vivo; hence, we investigated the effect of sesamin on HNSCC cells in vitro. Methods and Results: Sesamin-treated human oral cancer cell lines FaDu, HSC-3, and Ca9-22 were subjected to a wound-healing assay. Furthermore, Western blotting was performed to assess the effect of sesamin on the expression levels of matrix metalloproteinase (MMP)-2 and proteins of the MAPK signaling pathway, including p-ERK1/2, P-p38, and p-JNK1/2. In addition, we investigated the association between MMP-2 expression and the MAPK pathway in sesamin-treated oral cancer cells. Sesamin inhibited cell migration and invasion in FaDu, Ca9-22, and HSC-3 cells and suppressed MMP-2 at noncytotoxic concentrations (0 to 40 μM). Furthermore, sesamin significantly reduced p38 MAPK and JNK phosphorylation in a dose-dependent manner in FaDu and HSC-3 cells. Conclusions: These results indicate that sesamin suppresses the migration and invasion of HNSCC cells by regulating MMP-2 and is thus a potential antimetastatic agent for treating HNSCC.

Homeobox-A13 acts as a functional prognostic and diagnostic biomarker via regulating P53 and Wnt signaling pathways in lung cancer

2021 ◽  
pp. 1-16
Author(s):  
Yang Wang ◽  
Bo He ◽  
Yan Dong ◽  
Gong-Jin He ◽  
Xiao-Wei Qi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Signaling Pathways ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Clinical Feature ◽  
Diagnostic Biomarker

BACKGROUND: The prognosis of lung cancer patients is poor without useful prognostic and diagnostic biomarker. To search for novel prognostic and diagnostic markers, we previously found homeobox-A13 (HOXA13) as a promising candidate in lung cancer. OBJECTIVE: To determine the precisely clinical feature, prognostic and diagnostic value, possible role and mechanism of HOXA13. METHODS: Gene-expression was explored by real-time quantitative-PCR, western-blot and tissue-microarray. The associations were analyzed by Chi-square test, Kaplan-Meier and Cox-regression. The roles and mechanisms were evaluated by MTS, EdU, transwell, xenograft tumor and luciferase-reporter assays. RESULTS: HOXA13 expression is increased in tumors, and correlated with age of patients. HOXA13 expression is associated with unfavorable overall survival and relapse-free survival of patients in four cohorts. Interestingly, HOXA13 has different prognostic significance in adenocarcinoma (ADC) and squamous-cell carcinoma (SCC), and is a sex- and smoke-related prognostic factor only in ADC. Importantly, HOXA13 can serve as a diagnostic biomarker for lung cancer, especially for SCC. HOXA13 can promote cancer-cell proliferation, migration and invasion in vitro, and facilitate tumorigenicity and tumor metastasis in vivo. HOXA13 acts the oncogenic roles on tumor growth and metastasis by regulating P53 and Wnt/β-catenin signaling activities in lung cancer. CONCLUSIONS: HOXA13 is a new prognostic and diagnostic biomarker associated with P53 and Wnt/β-catenin signaling pathways.

scholarly journals THAP9-AS1/miR-133b/SOX4 positive feedback loop facilitates the progression of esophageal squamous cell carcinoma

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Jiwei Cheng ◽  
Haibo Ma ◽  
Ming Yan ◽  
Wenqun Xing
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Malignant Tumors ◽  
Migration And Invasion ◽  
Positive Feedback Loop

AbstractEsophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in the digestive system with a high incidence and poor prognosis. Long non-coding RNAs (LncRNA) have been reported to be closely associated with the occurrence and development of various human cancers. Data from GSE89102 shows an increase of THAP9-AS1 expression in ESCC. However, its functions and mechanisms underlying ESCC progression remain to be investigated. In this study, we found that THAP9-AS1 was overexpressed in ESCC tissues and cells. High THAP9-AS1 expression was positively correlated with tumor size, TNM stage, lymph node metastasis, and worse prognosis. Functionally, depletion of THAP9-AS1 suppressed cell proliferation, migration, and invasion, while enhanced apoptosis in vitro. Consistently, knockdown of THAP9-AS1 inhibited xenograft tumor growth in vivo. Mechanistically, THAP9-AS1 could serve as a competing endogenous RNA (ceRNA) for miR-133b, resulting in the upregulation of SOX4. Reciprocally, SOX4 bound to the promoter region of THAP9-AS1 to activate its transcription. Moreover, the anti-tumor property induced by THAP9-AS1 knockdown was significantly impaired due to miR-133b downregulation or SOX4 overexpression. Taken together, our study reveals a positive feedback loop of THAP9-AS1/miR-133b/SOX4 to facilitate ESCC progression, providing a potential molecular target to fight against ESCC.

scholarly journals Podoplanin interaction with caveolin-1 promotes tumour cell migration and invasion

2018 ◽  
Author(s):  
Luisa Pedro ◽  
Jacqueline D. Shields
Keyword(s):  
Tumour Cell ◽  
Surface Expression ◽  
Alveolar Epithelial Cells ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Caveolin 1 ◽  
Alveolar Epithelial ◽  
Podoplanin Expression

AbstractPodoplanin, a highly O-glycosylated type-1 transmembrane glycoprotein, found in lymphatic endothelial cells, podocytes, alveolar epithelial cells and lymph node fibroblasts is also expressed by tumour cells, and is correlated with more aggressive disease. Despite numerous studies documenting podoplanin expression, the mechanisms underlying its tumour-promoting functions remain unclear. Using a murine melanoma cell line that endogenously expresses podoplanin, we demonstrate interactions with proteins necessary for cytoskeleton reorganization, adhesion and matrix degradation, and endocytosis/receptor recycling but also identify a novel interaction with caveolin-1. We generated a panel of podoplanin and caveolin-1 variants to determine the molecular interactions and functional consequences of these interactions. Complementary in vitro and in vivo systems confirmed the existence of a functional cooperation in which surface expression of both full length, signalling competent podoplanin and caveolin-1 are necessary to induce directional migration and invasion, which is executed via PAK1 and ERK1 pathways. Our findings establish that podoplanin signalling mediates the invasive properties of melanoma cells in a caveolin-1 dependent manner.Summary StatementThis manuscript describes a new interaction and functional cooperation between podoplanin and caveolin1 that drives tumour cell invasion into surrounding tissues.

scholarly journals circATP2A2 promotes osteosarcoma progression by upregulating MYH9

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 1749-1761
Author(s):  
Xin Cao ◽  
Xianfeng Meng ◽  
Peng Fu ◽  
Lin Wu ◽  
Zhen Yang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Area Under Curve ◽  
Prognostic Biomarker ◽  
Migration And Invasion ◽  
Promising Target ◽  
Repressive Effect ◽  
Cell Malignancy

Abstract Osteosarcoma (OS) is a highly metastatic primary malignant tumor. CircRNA hsa_circ_0028173 (circATP2A2) has been uncovered to be related to the advancement of OS. However, the biological role of circATP2A2 in OS has not been validated. circATP2A2 and MYH9 were upregulated while miR-335-5p was downregulated in OS. OS patients with high circATP2A2 expression displayed a shorter overall survival and the area under curve of circATP2A2 was 0.77, manifesting that circATP2A2 might be a diagnostic and prognostic biomarker. circATP2A2 silencing repressed OS cell proliferation and glycolysis in vivo and constrained OS cell proliferation, glycolysis, migration, and invasion in vitro. circATP2A2 regulated MYH9 expression through sponging miR-335-5p. MiR-335-5p inhibitor reversed the repressive effect of circATP2A2 knockdown on OS cell malignancy and glycolysis. MYH9 overexpression overturned miR-335-5p upregulation-mediated OS cell malignancy and glycolysis. circATP2A2 accelerated OS cell malignancy and glycolysis through upregulating MYH9 via sponging miR-335-5p, offering a promising target for OS treatment.

scholarly journals Human Wharton’s jelly stem cells inhibit endometriosis through apoptosis induction

Reproduction ◽  
2020 ◽  
Vol 159 (5) ◽  
pp. 549-558 ◽  
Author(s):  
Saba Hajazimian ◽  
Masoud Maleki ◽  
Shahla Danaei Mehrabad ◽  
Alireza Isazadeh
Keyword(s):  
Stem Cells ◽  
Colony Formation ◽  
Wharton’S Jelly ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Morphological Alterations ◽  
Wharton's Jelly ◽  
Genes Expression ◽  
Induction Of Apoptosis

Endometriosis is a relatively benign disease characterized by endometrial tumors and uterus stroma. Apoptosis suppression is one of the most important pathological processes of endometriosis. Recently, several studies reported that human Wharton’s jelly stem cells (hWJSCs) can inhibit growth and proliferation of various cancer cells through induction of apoptosis. Therefore, the aim of the present study was to investigate the effects of hWJSCs conditioned medium (hWJSC-CM) and cell-free lysate (hWJSC-CL) on endometriosis cells in vitro. In the present study, effects of different concentrations of hWJSC-CM and hWJSC-CL on viability and proliferation, morphological alterations, colony formation, migration, invasion, and apoptosis of endometriosis cells were evaluated. Our results showed that hWJSC-CM and hWJSC-CL decrease viability and proliferation, colony formation, migration, and invasion, as well as increase morphological alterations and apoptosis of endometriosis cells, in a concentration- and time-dependent manner. Decreased migration and invasion of treated endometriosis cells with hWJSC-CM and hWJSC-CL may be due to decrease of MMP-2 and MMP-9 gene expression. Moreover, induction of apoptosis in treated endometriosis cells can be due to regulation of apoptosis-related genes expression, including BAX, BCL-2, SMAC, and SURVIVIN. The results of the present study suggest that hWJSC-CM and hWJSC-CL can inhibit endometriosis cells at a mild-to-moderate level through various physiological mechanisms. However, further studies on animal models are necessary to achieve more accurate results.

scholarly journals Curcumol inhibits malignant biological behaviors and TMZ-resistance of glioma cells via reducing long noncoding RNA FoxD2-As1 promoted EZH2 activation

2021 ◽  
Author(s):  
Xuyang Lv ◽  
Jiangchuan Sun ◽  
Linfeng Hu ◽  
Ying Qian ◽  
Chunlei Fan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Noncoding Rna ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Self Renewal

Abstract Background: Although curcumol has been shown to possess antitumor effects in several cancers, its effects on glioma are largely unknown. Recently, lncRNAs have been reported to play an oncogenic role through epigenetic modifications. Therefore, here, we investigated whether curcumol inhibited glioma progression by reducing FOXD2-AS1-mediated enhancer of zeste homolog 2 (EZH2) activation.Methods: MTT, colony formation, flow cytometry, Transwell, and neurosphere formation assays were used to assess cell proliferation, cell cycle, apoptosis, the percentage of CD133+ cells, the migration and invasion abilities, and the self-renewal ability. qRT-PCR, western blotting, immunofluorescence, and immunohistochemical staining were used to detect mRNA and protein levels. Isobologram analysis and methylation-specific PCR were used to analyze the effects of curcumol on TMZ resistance in glioma cells. DNA pull-down and Chip assays were employed to explore the molecular mechanism underlying the functions of curcumol in glioma cells. Tumorigenicity was determined using a xenograft formation assay. Results: Curcumol inhibited the proliferation, metastasis, self-renewal ability, and TMZ resistance of glioma cells in vitro and in vivo. FOXD2-AS1 was highly expressed in glioma cell lines, and its expression was suppressed by curcumol treatment in a dose- and time-dependent manner. The forced expression of FOXD2-AS1 abrogated the effect of curcumol on glioma cell proliferation, metastasis, self-renewal ability, and TMZ resistance. Moreover, the forced expression of FOXD2-AS1 reversed the inhibitory effect of curcumol on EZH2 activation.Conclusions: We showed for the first time that curcumol is effective in inhibiting malignant biological behaviors and TMZ-resistance of glioma cells by suppressing FOXD2-AS1-mediated EZH2 activation on anti-oncogenes. Our findings offer the possibility of exploiting curcumol as a promising therapeutic agent for glioma treatment and may provide an option for the clinical application of this natural herbal medicine.

scholarly journals Increased Thioredoxin-1 Expression Promotes Cancer Progression and Predicts Poor Prognosis in Patients with Gastric Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Wenjing Shang ◽  
Zhongdong Xie ◽  
Fengying Lu ◽  
Daoquan Fang ◽  
Tianbin Tang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Growth ◽  
Poor Prognosis ◽  
Prognostic Significance ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Antitumor Effects ◽  
Thioredoxin 1

Background. Thioredoxin-1 (Trx-1) is a small redox protein, which plays an important role in many biological processes. Although increased expression of Trx-1 in various solid tumors has been reported, the prognostic significance and function of Trx-1 in human gastric cancer (GC) are still unclear. Here, we investigated the clinical and prognostic significance of Trx-1 expression and the function and mechanism of Trx-1 in human GC. Methods. We analyzed Trx-1 mRNA expression from the GEO database and Trx-1 protein expression in 144 GC tissues using immunohistochemistry. Effects of Trx-1 on GC cell were assessed in vitro and in vivo through Trx-1 knockdown or overexpression. The antitumor effects of the Trx-1 inhibitor, PX-12, on GC cells were investigated. PTEN and p-AKT expressions were evaluated by Western blotting. Results. Increased Trx-1 expression was found in GC tissues and associated with poor prognosis and aggressive clinicopathological characteristics in patients with GC. High Trx-1 expression predicted poor prognosis, and its expression was an independent prognostic factor for overall survival of GC patients. Knockdown of Trx-1 expression inhibited GC cell growth, migration, and invasion in vitro and tumor growth and lung metastasis in vivo. Conversely, overexpression of Trx-1 promoted GC cell growth, migration, and invasion. We also found that PX-12 inhibited GC cell growth, migration, and invasion. Overexpression of Trx-1 caused a decrease in PTEN and increase in p-AKT levels whereas silencing Trx-1 caused an increase in PTEN and decrease in p-AKT levels in GC cells. Inhibition of AKT signaling pathway by MK2206 also inhibited GC cell growth, migration, and invasion. Conclusion. Our results indicate that Trx-1 may be a promising prognostic indicator and therapeutic target for GC patients.

scholarly journals Enhanced Malignant Phenotypes of Glioblastoma Cells Surviving NPe6-Mediated Photodynamic Therapy are Regulated via ERK1/2 Activation

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3641
Author(s):  
Tatsuya Kobayashi ◽  
Makoto Miyazaki ◽  
Nobuyoshi Sasaki ◽  
Shun Yamamuro ◽  
Eita Uchida ◽  
...  
Keyword(s):  
Cell Death ◽  
Photodynamic Therapy ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Potential Therapeutic Target ◽  
Talaporfin Sodium ◽  
Polymerase Inhibitor ◽  
Human Gbm ◽  
Dose Dependent

To manage refractory and invasive glioblastomas (GBM)s, photodynamic therapy (PDT) using talaporfin sodium (NPe6) (NPe6-PDT) was recently approved in clinical practice. However, the molecular machineries regulating resistance against NPe6-PDT in GBMs and mechanisms underlying the changes in GBM phenotypes following NPe6-PDT remain unknown. Herein, we established an in vitro NPe6-mediated PDT model using human GBM cell lines. NPe6-PDT induced GBM cell death in a NPe6 dose-dependent manner. However, this NPe6-PDT-induced GBM cell death was not completely blocked by the pan-caspase inhibitor, suggesting NPe6-PDT induces both caspase-dependent and -independent cell death. Moreover, treatment with poly (ADP-ribose) polymerase inhibitor blocked NPe6-PDT-triggered caspase-independent GBM cell death. Next, it was also revealed resistance to re-NPe6-PDT of GBM cells and GBM stem cells survived following NPe6-PDT (NPe6-PDT-R cells), as well as migration and invasion of NPe6-PDT-R cells were enhanced. Immunoblotting of NPe6-PDT-R cells to assess the behavior of the proteins that are known to be stress-induced revealed that only ERK1/2 activation exhibited the same trend as migration. Importantly, treatment with the MEK1/2 inhibitor trametinib reversed resistance against re-NPe6-PDT and suppressed the enhanced migration and invasion of NPe6-PDT-R cells. Overall, enhanced ERK1/2 activation is suggested as a key regulator of elevated malignant phenotypes of GBM cells surviving NPe6-PDT and is therefore considered as a potential therapeutic target against GBM.

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