P11 KRT17 PROMOTES PROLIFERATION AND METASTASIS OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA LEADING TO POOR PROGNOSIS

2019 ◽  
Vol 32 (Supplement_2) ◽  
Author(s):  
Liu Zhun ◽  
Shen Zhimin ◽  
Zhang Peipei ◽  
Yu Shaobin ◽  
Gao Lei ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Prognostic Significance ◽  
Predictive Biomarker ◽  
Vital Role ◽  
Migration And Invasion ◽  
Depth Of Invasion ◽  
Node Metastasis ◽  
Proliferation And Metastasis ◽  
Migration Capacity

Abstract Background Keratin17(KRT17), as a multifunction cytoskeletal protein, associated with a multitudinous of biological processes, including cell proliferation, migration, and invasion. Previously, we have found overexpression of KRT17 genes in ESCC tissues. Currently, published kinds of researches claimed KRT17 is engaged in the tumorigenesis and progression of multiple cancers. However, the prognostic significance of KRT17 in ESCC patients and its effects in ESCC progression remain indistinct. Methods We verified the expression of KRT17 in ESCC tissues by Western blotting and q-PCR. And then the immunochemistry was performed to investigate the KRT17 expression in 64 ESCC tissue specimens. KRT17 upregulated, and knockdown EC9706 and Eca109 cells were constructed by Lentivirus overexpression and CRISPR-Cas9. The function of KRT17 in ESCC proliferation and metastasis were studied by CCK-8 assays, plate colony formation assays, trans-well and wound healing in vitro. Results overexpression of KRT17 was verified in 12 pairs of fresh ESCC tissues. We found that the expression of KRT17 was remarkably positively correlated with the depth of invasion (T) (P<0.05), lymph node metastasis (N) (P<0.05), tumor node metastasis (TNM) stage (P<0.0001). High expression of KRT17 predicted a lower 5-year survival rate(P<0.001) of ESCC patients. We verified the KRT17 malignant behavior of ESCC in vitro. We conformed proliferation and migration capacity of ESCC were significantly enhanced by overexpression of KRT17 but compromised when KRT17 was knocked down. Collectively, it supported that the increased expression of KRT17 promoted proliferation and migratory phenotype of ESCC. Conclusion The breakthrough indicated that the upregulation of KRT17 in ESCC is closely related to malignant progression, our findings revealed that KRT17 plays a vital role in facilitating proliferation and metastasis, and could be used as a novel predictive biomarker, thus providing a novel diagnosis and therapeutic target for ESCC patients. Keywords: Molecular target ESCC Keratin17 Therapeutic target

scholarly journals Hypoxia Promotes Metastasis of Gastric Cancer Through ANXA1 Pathway

2021 ◽  
Author(s):  
Qing-Hua Liu ◽  
Lei Xia ◽  
Xiao-Yue Wu ◽  
Chen-Chen Lu ◽  
Jing-Yuan Song ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Prognostic Factor ◽  
Therapeutic Target ◽  
Prognostic Markers ◽  
Migration And Invasion ◽  
Annexin A1 ◽  
Node Metastasis ◽  
Hif Pathway

Abstract Background: To determinethe involvement of hypoxia inducible factor1α (HIF) pathway inmetastasis of gastric cancer (GC). Method: It was determined that the expression of HIF and annexin A1 (ANXA1) in human GC (n=76),using immunohis to chemistry, as well as,the involvement of HIF pathway in GC cell migration and invasion in vitro. The correlation between HIF/ANXA1 and the prognosis wasalso evaluated.Results: HIF1αwas substantiallyupregulatedin GC tissues, compared to that of non-cancer. HIF1α was positively correlated withlymph node metastasis, but inversely correlated with survival in GC patients. HIF1αwas an independent prognostic factor in GC patients, and the combination of HIF1α and ANXA1 might serve asuseful prognostic markers in GCpatients.Furthermore,HIF-1αseems topromote GC migration and invasion through HIF1α/ANXA1/MMP-2 pathway. Conclusions: Our findings suggestthat HIF-1αmay serve as a promising prognostic biomarkerand therapeutic target for inhibiting GC metastasis.

scholarly journals miR-136 Inhibits Malignant Progression of Hepatocellular Carcinoma Cells by Targeting Cyclooxygenase 2

2018 ◽  
Vol 26 (6) ◽  
pp. 967-976 ◽  
Author(s):  
Haiyan Jia ◽  
Hong Wang ◽  
Yanfen Yao ◽  
Chunlei Wang ◽  
Pibao Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Vital Role ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Reporter Assay ◽  
Vitro Assay ◽  
Proliferation And Metastasis ◽  
Relationship Of

MicroRNAs (miRNAs) play a vital role in regulating tumor progression. Dysregulated miR-136 expression was linked to the development of various human cancers. In the present study, we investigated the expression and relationship of miR-136 and COX2 in hepatocellular carcinoma (HCC) using relevant experiments, involving CCK-8, Transwell assay, and luciferase reporter assay. We demonstrated that miR-136 expression is obviously decreased in HCC tissues and cells, and negatively correlated with the expression of COX2 mRNA. In vitro assay revealed that overexpression of miR-136 significantly changed the expression of proliferation- and metastasis-related proteins and inhibited the proliferation, migration, and invasion of HepG2 and Hep3B cells. Dual-luciferase reporter assay validated that the 3′-untranslated region (3′-UTR) of COX2 is a direct target of miR-136. Furthermore, COX2 siRNA partially enhanced the miR-136 overexpression-induced inhibitory effects. In conclusion, miR-136 was vital in the regulation of HCC cell proliferation and metastasis by targeting COX2. Thus, our findings provided novel evidence that miR-136 might be recommended as a potential target for the diagnosis and treatment of HCC patients.

P8 KERATIN 17 PROMOTES CELLS PROLIFERATION AND METASTASIS IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

2019 ◽  
Vol 32 (Supplement_2) ◽  
Author(s):  
Liu Zhun ◽  
Shen Zhimin ◽  
Zhang Peipei ◽  
Yu Shaobin ◽  
Gao Lei ◽  
...  
Keyword(s):  
Wound Healing ◽  
Colony Formation ◽  
Prognostic Significance ◽  
Migration And Invasion ◽  
Migration Ability ◽  
Chamber Experiment ◽  
Proliferation And Metastasis ◽  
The Impact

Abstract Background Keratin17(KRT17), as a multifunction cytoskeletal protein, associated with a multitudinous of biological processes, including cell proliferation, migration, and invasion. Previously, we have found up-expression of KRT17 genes in ESCC tissues. Currently, published kinds of researches claimed KRT17 is engaged in the tumorigenesis and progression of multiple cancers. However, the prognostic significance of KRT17 in ESCC patients and its effects in ESCC progression remains indistinct. Methods We verified the expression level of KRT17 in ESCC tissues by Western blotting and q-PCR and constructed KRT17 upregulated and knockdown EC9706 and Eca109 cells by Lentivirus overexpression and CAS9. The function of KRT17 in ESCC proliferation and metastasis were studied in vitro. We performed CCK-8 assays and plate colony formation assays and the plate colony formation assays to explore the effect of KRT17 on the proliferation, Moreover, the trans-well migration chamber experiment and wound healing test was taken to reveal the impact of KRT17 on migration capabilities. Results We verified that KRT17 is overexpressed in ESCC tissues and the role of KRT17 in the malignant behavior of ESCC in vitro and vivo . In CCK-8 assays and plate colony formation assays. We conformed proliferation capacity was notably enhanced by overexpression of KRT17 but compromised when KRT17 was knocked out. On the other hand, we used the plate colony formation assays to explore the effect of KRT17 on the proliferation of ESCC cells. KRT17 up-regulated significantly strengthened the proliferation while the KRT17 knockdown was weakened. To reveal the impact of KRT17 on migration, the trans-well migration chamber experiment was used to compare the role of down-regulation and up-regulation of KRT17 in migration; the results demonstrated that reducing expression of KRT17 significantly blocked the movement of ESCC cells as compared with the empty vector control. Otherwise, it has been confirmed that the cell migration ability employs a wound healing/scratch test because wound closure is generally a measure of cell motility. The results showed KRT17 overexpression notably reinforced the mobility of ESCC cells compared with the empty groups, whereas KRT17 knockdown cells prolonged the time to close the injury compared to blank groups. Collectively, these discoveries support that the increased expression of KRT17 in ESCC cells promoted a more proliferation and migratory phenotype in vitro. Conclusion The breakthrough indicated that the up-regulation of KRT17 in ESCC is closely related to malignant progression. Our data confirmed that KRT17 plays an essential role in reinforcing proliferation and metastasis in ESCC. Thence, KRT17 may serve as a significant molecular target for the diagnosis and therapy of ESCC.

scholarly journals HDAC4 promotes nasopharyngeal carcinoma progression and serves as a therapeutic target

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Chun Cheng ◽  
Jun Yang ◽  
Si-Wei Li ◽  
Guofu Huang ◽  
Chenxi Li ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Tumor Growth ◽  
Therapeutic Target ◽  
Histone Deacetylases ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
E Cadherin

AbstractHistone deacetylases (HDACs) are involved in tumor progression, and some have been successfully targeted for cancer therapy. The expression of histone deacetylase 4 (HDAC4), a class IIa HDAC, was upregulated in our previous microarray screen. However, the role of HDAC4 dysregulation and mechanisms underlying tumor growth and metastasis in nasopharyngeal carcinoma (NPC) remain elusive. Here, we first confirmed that the HDAC4 levels in primary and metastatic NPC tissues were significantly increased compared with those in normal nasopharyngeal epithelial tissues and found that high HDAC4 expression predicted a poor overall survival (OS) and progression-free survival (PFS). Functionally, HDAC4 accelerated cell cycle G1/S transition and induced the epithelial-to-mesenchymal transition to promote NPC cell proliferation, migration, and invasion in vitro, as well as tumor growth and lung metastasis in vivo. Intriguingly, knockdown of N-CoR abolished the effects of HDAC4 on the invasion and migration abilities of NPC cells. Mechanistically, HDAC3/4 binds to the E-cadherin promoter to repress E-cadherin transcription. We also showed that the HDAC4 inhibitor tasquinimod suppresses tumor growth in NPC. Thus, HDAC4 may be a potential diagnostic marker and therapeutic target in patients with NPC.

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.

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 Lactate secreted by PKM2 upregulation promotes Galectin-9-mediated immunosuppression via inhibiting NF-κB pathway in HNSCC

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Hanyue Chang ◽  
Qiaoshi Xu ◽  
Jiayi Li ◽  
Mingyu Li ◽  
Zhiyuan Zhang ◽  
...  
Keyword(s):  
Critical Role ◽  
Lactate Production ◽  
Metabolic Reprogramming ◽  
Migration And Invasion ◽  
Histone Deacetylase 3 ◽  
Proliferation And Metastasis ◽  
Immunosuppressive Microenvironment ◽  
Transcriptional Complex

AbstractPyruvate kinase M2 as a key rate-limiting enzyme in glycolysis, it plays a critical role in metabolic reprogramming and carcinogenesis. However, whether PKM2 can promote immunosuppressive microenvironment formation remains unknown in head and neck squamous cell carcinoma (HNSCC). PKM2 expression was detected using immunohistochemical staining. The biological functions of PKM2 were investigated in vitro and in vivo. Lactate production and the expression of Galectin-9, a critical immunosuppression molecule, were detected after PKM2 knockdown and overexpression in HNSCC cells. The mechanism of lactate regulating Galectin-9 expression through NF-κB signaling was explored in vitro. Overexpression of PKM2 correlates with poor prognosis in HNSCC patients. Silencing PKM2 markedly inhibits proliferation and metastasis capacity in vivo and in vitro, and vice versa. The glycolysis and glycolytic capacity are significantly decreased after PKM2 silencing. Lactate secretion induced by PKM2 significantly promotes migration and invasion capacity. Furthermore, a positive correlation between PKM2 and Galectin-9 expression is observed in HNSCC tissues. The induction of Galectin-9 expression by PKM2 can be affected by a lactate transporter inhibitor. Mechanically, lactate impeded the suppressive transcriptional complex formation of NF-κB and histone deacetylase 3 (HDAC3), which released the transcription of Galectin-9 mediated by NF-κB signaling. Our findings demonstrate that lactate produced by PKM2 upregulation promotes tumor progression and Galectin-9-mediated immunosuppression via NF-κB signaling inhibition in HNSCC, which bridges metabolism and immunosuppression. The novel PKM2-lactate-Galectin-9 axis might be a potential therapeutic target in HNSCC.

scholarly journals Serum exosomal miR-4787-3p as potential lymph node metastasis and prognostic marker in esophageal squamous cell carcinoma.

2021 ◽  
Author(s):  
Shuang Liu ◽  
Zheng Lin ◽  
Jianwen Wang ◽  
Zerong Zheng ◽  
Wenqing Rao ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cox Regression ◽  
High Serum ◽  
Migration And Invasion ◽  
Cox Regression Analysis ◽  
Mirna Array ◽  
Node Metastasis

Abstract Background: To explore the miR-4787-3p expression levels in the serum exosome and tissue and its role in lymph node metastasis and prognosis in ESCC. Methods: The miRNA array was conducted to detect the ESCC serum exosomal miRNAs expression. A receiver operating characteristic (ROC) curve was constructed to determine the predictive ESCC with lymph node metastasis efficacy of serum exosomal miR-4784-3p. The Cox regression analysis was preformed to explore prognostic factors for ESCC. Transwell assay and CCK-8 assays were utilized to evaluate cell migration, invasion, and proliferation, respectively. Results: High serum exosomal miR-4787-3p expression was demonstrated in lymph node metastasis group (P =0.011). The serum exosomal miR-4787-3p expression was significantly associated with histologic grade (P = 0.010), and TNM stage (P = 0.033). However, there was no significant relationship between tissue miR-4787-3p expression and clinical characteristics (P >0.05). ROC analyses revealed that the AUCs of serum exosomal miR-4787-3p for lymph node metastasis prediction was 0.787. The Cox regression analysis found that high expression serum exosomal miR-4787-3p were correlated with poor prognoses (for OS, HR=2.68, 95% CI: 1.02~7.04; for DFS, HR = 2.65, 95% CI: 1.05~6.68). Nevertheless, no association between tissue miR-4787-3p expression and ESCC prognosis. In addition, upregulated expression of miR-4787-3p could promote migration and invasion in vitro. Conclusions: Serum exosomal miR-4787-3p can be promising biomarkers for ESCC metastasis and prognosis

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 Downregulation of PTPRK Promotes Cell Proliferation and Metastasis of NSCLC by Enhancing STAT3 Activation

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Xuting Xu ◽  
Dong Li ◽  
Jin Liu ◽  
Zhihong Ma ◽  
Huilian Huang ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Tumor Suppressor ◽  
Cell Lines ◽  
Western Blotting ◽  
Invasion And Migration ◽  
Node Metastasis ◽  
Proliferation And Metastasis ◽  
And Migration

Objective. The receptor-type tyrosine-protein phosphatase κ (PTPRK) is a candidate tumor suppressor involved in the tumorigenesis of various organs. However, its expression and biological roles in non-small-cell lung cancer (NSCLC) have not yet been investigated. Methods. PTPRK expression in NSCLC tissues and cell lines was examined using real-time PCR and western blotting. In addition, the effects of PTPRK on cell migration, invasion, and proliferation were evaluated in vitro. Furthermore, we explored whether the downregulation of PTPRK led to STAT3 activation in NSCLC cell lines by western blotting. The expression of phospho-STAT3Tyr705 in primary human NSCLC tissues was evaluated by immunohistochemistry. Results. The results showed that PTPRK expression was frequently reduced in NSCLC tissues with lymph node metastasis and cell lines. The inhibition of PTPRK expression resulted in increased proliferation, invasion, and migration of NSCLC cells in vitro. Additionally, after silencing of PTPRK, phospho-STAT3Tyr705 was significantly increased in NSCLC cells. Moreover, the phospho-STAT3Tyr705 levels of NSCLC tissues were positively correlated with lymph node metastasis and significantly inversely correlated with the expression of PTPRK (p<0.05). Conclusions. These results suggested that PTPRK functions as a novel tumor suppressor in NSCLC, and its suppressive ability may be involved in STAT3 activation.

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