scholarly journals LncRNA-ENST00000543604 Exerts a Tumor-Promoting Effect via miRNA 564/AEG1 or ZNF326/EMT and Predicts The Prognosis of and Chemotherapeutic Effect in Colorectal Cancer

2021 ◽  
Author(s):  
Weimin Wang ◽  
Zhen Zhou ◽  
Xiaojun Dai ◽  
Haibo Wang ◽  
Jun Jin ◽  
...  
Keyword(s):  
High Throughput Sequencing ◽  
Cox Regression ◽  
Promoting Effect ◽  
Qrt Pcr ◽  
Kaplan Meier ◽  
Signaling Axis ◽  
Proliferation And Metastasis ◽  
Chemotherapy Efficacy

Abstract Background:Colorectal cancer is a common malignant tumor. Recent studies have found that lncRNAs play an important role in the occurrence and development of colorectal cancer.Methods:Based on high-throughput sequencing results of fresh CRC tissues and adjacent tissues, we identified lncRNA-ENST00000543604 (lncRNA 604) as the research object by qRT-PCR in CRC tissues and cells. The FISH method was used to detect the location of lncRNA 604 in cells, and its expression was detected on a tissue chip. We explored the mechanism of lncRNA 604 action by using luciferin reporter, qRT-PCR and Western blot assays. Kaplan-Meier survival analysis and a Cox regression model were used to analyze the correlation of lncRNA 604 and its regulatory molecules with the prognosis of and chemotherapy efficacy in CRC patients.Results:In this study, we found that the expression levels of lncRNA 604 were increased in CRC. LncRNA 604 could promote CRC cell proliferation and metastasis through the miRNA 564/AEG-1 or ZNF326/EMT signaling axis in vivo and in vitro. LncRNA 604 could predict the prognosis of CRC and was an independent negative factor. LncRNA 604 exerted a synergistic effect with miRNA 564 or ZNF326 on the prognosis of CRC. LncRNA 604 could improve chemoresistance by increasing the expression of AEG-1, NF-κB, and ERCC1.Conclusions:Our study demonstrated that lncRNA 604 could promote the progression of CRC via the lncRNA 604/miRNA 564/AEG-1/EMT or lncRNA 604/ZNF326/EMT signaling axis. LncRNA 604 is an independent and effective molecule for predicting the prognosis of CRC. LncRNA 604 could improve chemoresistance by increasing drug resistance protein expression.

scholarly journals HN1 Promotes Proliferation, Metastasis and Attenuates the Chemosensitivity of HCC Cells to Oxaliplatin by Inhibiting Degradation of HMGB1 Through Interacting With TRIM28

2021 ◽  
Author(s):  
Ruhua Wang ◽  
Yunong Fu ◽  
Menglin Yao ◽  
Xiaomeng Cui ◽  
Yan Zhao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Dna Lesions ◽  
Advanced Hepatocellular Carcinoma ◽  
Promoting Effect ◽  
Proliferation And Metastasis ◽  
Cell Proliferation And Metastasis ◽  
Hcc Cells

Abstract Background: The oxaliplatin-based chemotherapy has revealed an encouraging therapeutic efficacy for advanced hepatocellular carcinoma patients. However, the development of resistance limits its clinical utilization. In addition, the chemotherapy resistance in HCC is usually accompanied with other malignant phenotypes, such as cell proliferation and metastasis, which together result in poor prognosis of HCC patients. Therefore, efforts should be made to explore potential regulators which fuel multiple events of HCC progression.Methods: The qRT-PCR, western blot, immunohistochemistry and immunofluorescence were performed to measure mRNA and protein expression. MTT assay, colony formation and Transwell assay were performed to evaluate cell proliferation and metastasis. Flow cytometry was performed to test cell apoptosis. Alkaline Comet assay was performed to measure DNA lesions. Transmission electron microscope analysis provided potent testimony of autophagy. The role of HN1 on the malignant phenotypes of hepatoma carcinoma was demonstrated in vitro and in vivo.Results: The immunohistochemistry analysis of HCC patient tissues revealed that the expression of HN1 was higher in HCC tissues compared to adjacent tissues and was associated with worse prognosis. In vitro, HN1 knockdown inhibited proliferation and metastasis of HCC cells, whereas HN1 overexpression promoted their proliferation and metastasis. In addition, we found that HN1 knockdown sensitized HCC cells to oxaliplatin, which is companied with deteriorated DNA damage and increased cell apoptosis in oxaliplatin-treated HCC cells. In vivo, HN1 knockdown inhibited the tumor growth and metastasis, and promoted the anti-cancer efficiency of oxaliplatin. Mechanically, HN1 prevented HMGB1 from ubiquitination and degradation via autophagy-lysosome pathway, which is related to its interaction with TRIM28, and overexpression of HMGB1 can restore the malignant phenotypes of HN1 knockdown in HCC cells. Furthermore, we found that HN1 can regulate cellular autophagy via HMGB1, which is important to tumor-promoting effect of HN1.Conclusions: In conclusion, we systemically revealed the multiple functions of HN1 in HCC progression and the underlying molecular mechanism, which indicated that HN1 could be a promising therapeutic target for HCC treatment.

scholarly journals KDM6B promotes ESCC cell proliferation and metastasis by facilitating C/EBPβ transcription

2020 ◽  
Author(s):  
Mei Qin ◽  
Fei Han ◽  
Jian Wu ◽  
Feng-xia Gao ◽  
Yuan Li ◽  
...  
Keyword(s):  
Transcriptional Activity ◽  
Rna Seq ◽  
Functional Tests ◽  
Qrt Pcr ◽  
Node Metastasis ◽  
Demethylase Activity ◽  
Proliferation And Metastasis ◽  
Cell Proliferation And Metastasis

Abstract Background: As an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression, KDM6B has been implicated in the development and malignant progression in various types of cancers. However, its potential roles in esophageal squamous cell carcinoma (ESCC) have not been explored.Methods: The expression of KDM6B in human ESCC tissues and cell lines was examined using qRT-PCR, immunohistochemical staining and immunoblotting. The effects of KDM6B on the proliferation and metastasis of ESCC were examined using in vitro and in vivo functional tests. RNA-seq and ChIP-seq assay were used to demonstrate the molecular biological mechanism of KDM6B in ESCC.Results: We show that the expression level of KDM6B increased significantly in patients with lymph node metastasis. KDM6B knockdown reduces proliferation and metastasis of ESCC cells, while KDM6B overexpression has the opposite effects. Mechanistically, KDM6B regulates TNFA_SIGNALING_VIA_NFκB signalling pathways, and H3K27me3 binds to the promoter region of C/EBPβ, leading to the promotion of C/EBPβ transcription. Besides, we show that GSK-J4, a chemical inhibitor of KDM6B,markedly inhibits proliferation and metastasis of ESCC cells.Conclusions: KDM6B promotes ESCC progression by increasing the transcriptional activity of C/EBPβ depending on its H3K27 demethylase activity.

scholarly journals KDM6B Promotes ESCC Cell Proliferation and Metastasis by Facilitating C/EBPβ Transcription

2021 ◽  
Author(s):  
mei qin ◽  
fei han ◽  
jian wu ◽  
fengxia gao ◽  
yuan li ◽  
...  
Keyword(s):  
Transcriptional Activity ◽  
Rna Seq ◽  
Functional Tests ◽  
Qrt Pcr ◽  
Node Metastasis ◽  
Demethylase Activity ◽  
Proliferation And Metastasis ◽  
Cell Proliferation And Metastasis

Abstract BackgroundAs an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression, KDM6B has been implicated in the development and malignant progression in various types of cancers. However, its potential roles in esophageal squamous cell carcinoma (ESCC) have not been explored. MethodsThe expression of KDM6B in human ESCC tissues and cell lines was examined using qRT-PCR, immunohistochemical staining and immunoblotting. The effects of KDM6B on the proliferation and metastasis of ESCC were examined using in vitro and in vivo functional tests. RNA-seq and ChIP-seq assay were used to demonstrate the molecular biological mechanism of KDM6B in ESCC.ResultsWe show that the expression level of KDM6B increased significantly in patients with lymph node metastasis. Furthermore, we confirmed that KDM6B knockdown reduces proliferation and metastasis of ESCC cells, while KDM6B overexpression has the opposite effects. Mechanistically, KDM6B regulates TNFA_SIGNALING_VIA_NFκB signalling pathways, and H3K27me3 binds to the promoter region of C/EBPβ, leading to the promotion of C/EBPβ transcription. Besides, we show that GSK-J4, a chemical inhibitor of KDM6B, markedly inhibits proliferation and metastasis of ESCC cells. ConclusionsThe present study demonstrated that KDM6B promotes ESCC progression by increasing the transcriptional activity of C/EBPβ depending on its H3K27 demethylase activity.

scholarly journals GRHL3 Promotes Tumor Growth and Metastasis via the MEK Pathway in Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Lin Tan ◽  
Weiming Qu ◽  
Dajun Wu ◽  
Minji Liu ◽  
Qian Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Underlying Mechanism ◽  
Promoting Effect ◽  
Promote Tumor Growth ◽  
Proliferation And Metastasis ◽  
Tumor Growth And Metastasis ◽  
Cell Proliferation And Metastasis

GRHL3 is a factor associated with a tumor, of which the molecular mechanism remains a further investigation. We explored the underlying mechanism of tumor-promoting effect of GRHL3 in colorectal cancer (CRC), which is involved in the MEK1/2 pathway. The expression of GRHL3 was measured in CRC and adjacent normal tissue using qPCR and immunohistochemical staining. Lentivirus-mediated knockdown expression of GRHL3 was performed in the CRC cell line HT29. Cell proliferation and metastasis were assayed in vitro, and tumorigenicity was investigated in vivo. We found higher GRHL3 expression in colorectal cancer, which was negatively correlated with patients’ prognosis. Results from studies in vitro and in vivo indicated that downregulation of GRHL3 expression inhibited tumor growth and metastasis and inhibited the activation of the MEK1/2 pathway. The effect of GRHL3 downexpression was the same as that of MEK1/2 antagonists on suppression of tumor growth and metastasis. Our results suggested that GRHL3 may act as an oncogene to promote tumor growth and metastasis via the MEK pathway in colorectal cancer.

scholarly journals Overexpression of DSCR1 prevents proliferation and predicts favorable prognosis in colorectal cancer patients

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Wen-Xiang Li ◽  
Jia-Jia Zheng ◽  
Gang Zhao ◽  
Chen-Tao LYU ◽  
Wei-Qi Lu
Keyword(s):  
Cell Cycle ◽  
Overall Survival ◽  
Tumor Growth ◽  
Cox Regression ◽  
Survival Analyses ◽  
Cox Regression Analysis ◽  
Favorable Prognosis ◽  
Kaplan Meier

Abstract Objectives Down syndrome critical region 1 (DSCR1) is associated with carcinogenesis and tumor growth in several types of malignancy. However, little is known about the role of DSCR1 in CRC progression. The present study aimed to elucidate the clinicopathological significance, prognostic, and function roles of DSCR1 in CRC. Methods Firstly, we analyzed DSCR1 expression in 58 paired CRC samples and Oncomine database. Then, we analyzed DSCR1 expression in two independent CRC cohorts (test cohort: n = 70; validation cohort: n = 58) and tested its overall survival (OS) by Kaplan-Meier survival analyses. Finally, we overexpressed DSCR1 in two CRC cell lines DLD1 and LoVo and analyzed its effect on cell cycle and senescence. Results DSCR1 expression was significantly decreased in CRC samples and associated with clinicopathologic features of CRC patients, such as tumor size, lymph node metastasis, and TNM stage. CRC patients with low expression of DSCR1 had shorter overall survival (OS). Kaplan-Meier survival analyses showed that the expression of DSCR1 was significant factor for OS in both cohorts. Multiple Cox regression analysis showed that DSCR1 expression was an independent prognostic marker for OS in test cohort. Overexpression of DSCR1 isoform 4 (DSCR1-4) increased p21, p16, p-NFAT1, and p-NFAT2, while decreased CDK2, CDK4, and Cyclin D1 in CRC cells. In addition, overexpression of DSCR1-4 prevented proliferation and colony formation, and induced senescence in vitro. Moreover, overexpression of DSCR1-4 inhibited tumor growth and tumor angiogenesis in vivo. Conclusions Our study found high expression of DSCR1 contributes to favorable prognosis of CRC patients and prevents cell cycle and proliferation of CRC cells, indicating a critical tumor suppressive role in CRC progression.

scholarly journals SHCBP1 interacting with  EOGT enhanced O-GlcNAcylation of NOTCH1 and promoted the development of pancreatic cancer .

2020 ◽  
Author(s):  
Can Yang ◽  
Jianfei Hu ◽  
Qian Zhan ◽  
Zu-Wei Wang ◽  
Ge Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Developmental Disorders ◽  
High Throughput Sequencing ◽  
Cox Regression ◽  
Sh2 Domain ◽  
Migration And Invasion ◽  
Cox Regression Analysis ◽  
Xenograft Growth

Abstract Background: Pancreatic cancer(PDAC) remains one of the most lethal cancers worldwide, The accumulation of many abnormal epigenetic abnormalities contribute to the fatal prognosis of PDAC,While available studies are still limited. Many studies have confirmed that the Shc SH2-domain binding protein 1(SHCBP1) plays as proto-oncogene in cancers. However, whether SHCBP1 plays a role in pancreatic cancer oncogenesis is still unknown.EGF domain-specific O-linked GlcNActransferase (EOGT) acts as a key participant in the O-GlcNAcylation of NOTCH1. EOGT mutations inhibit the NOTCH1 signalling pathway and cause several congenital developmental disorders, However, the role of EOGT in malignancies has not been reported.Methods:SHCBP1 and EOGT were identified as proto-oncogenes in PDAC by High-throughput sequencing and Cox regression analysis,and validated by Internal and External cohort and public databases. The function of SHCBP1 and EOGT was determined in vitro and in vivo, The underlying mechanism was investigated by Western blot,Immunofluorescence（IF），Co-immunoprecipitation (Co-IP), Chromatin immunoprecipitation (ChIP)，and luciferase analyses.Results: The expression of EOGT and SHCBP1 was significantly elevated and correlated with worse prognosis in PDAC patients. In vitro, SHCBP1 overexpression promoted pancreatic cancer cell proliferation,migration and invasion, while knocking down SHCBP1 and EOGT inhibited these malignant processes. In vivo data showed that SHCBP1 overexpression promoted xenograft growth and lung metastasis and shortened survival in mice,whereas knocking down either EOGT or SHCBP1 expression suppressed xenograft growth and metastasis and prolonged survival. Morever，EOGT and SHCBP1 enhance the O-GlcNAcylation of NOTCH1, subsequently promoting the nuclear localization of the Notch intracellular domain (NICD) and inhibiting the transcription of E-cadherin and P21 in pancreatic cancer cells.Conclusion:All in all，This research revealed that SHCBP1 and EOGT act as proto-oncogenes in PDAC by enhancing the O-GlcNAcylation of NOTCH1，Which provides a new field of vision for new therapeutic targets for pancreatic cancer.

scholarly journals EphA2 super-enhancer promotes tumor progression by recruiting FOSL2 and TCF7L2 to activate the target gene EphA2

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Shuang Cui ◽  
Qiong Wu ◽  
Ming Liu ◽  
Mu Su ◽  
ShiYou Liu ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Tumor Cells ◽  
Target Gene ◽  
Super Enhancer ◽  
Proliferation And Metastasis ◽  
Active Transcription ◽  
Hct 116 ◽  
Large Clusters

AbstractSuper-enhancers or stretch enhancers (SEs) consist of large clusters of active transcription enhancers which promote the expression of critical genes that define cell identity during development and disease. However, the role of many super-enhancers in tumor cells remains unclear. This study aims to explore the function and mechanism of a new super-enhancer in various tumor cells. A new super-enhancer that exists in a variety of tumors named EphA2-Super-enhancer (EphA2-SE) was found using multiple databases and further identified. CRISPR/Cas9-mediated deletion of EphA2-SE results in the significant downregulation of its target gene EphA2. Mechanistically, we revealed that the core active region of EphA2-SE comprises E1 component enhancer, which recruits TCF7L2 and FOSL2 transcription factors to drive the expression of EphA2, induce cell proliferation and metastasis. Bioinformatics analysis of RNA-seq data and functional experiments in vitro illustrated that EphA2-SE deletion inhibited cell growth and metastasis by blocking PI3K/AKT and Wnt/β-catenin pathway in HeLa, HCT-116 and MCF-7 cells. Overexpression of EphA2 in EphA2-SE−/− clones rescued the effect of EphA2-SE deletion on proliferation and metastasis. Subsequent xenograft animal model revealed that EphA2-SE deletion suppressed tumor proliferation and survival in vivo. Taken together, these findings demonstrate that EphA2-SE plays an oncogenic role and promotes tumor progression in various tumors by recruiting FOSL2 and TCF7L2 to drive the expression of oncogene EphA2.

scholarly journals Cyr61 promotes Schwann cell proliferation and migration via αvβ3 integrin

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhenghui Cheng ◽  
Yawen Zhang ◽  
Yinchao Tian ◽  
Yuhan Chen ◽  
Fei Ding ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Peripheral Nerves ◽  
Molecular Mechanisms ◽  
Αvβ3 Integrin ◽  
Promoting Effect ◽  
Ccn Family ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Schwann cells (SCs) play a crucial role in the repair of peripheral nerves. This is due to their ability to proliferate, migrate, and provide trophic support to axon regrowth. During peripheral nerve injury, SCs de-differentiate and reprogram to gain the ability to repair nerves. Cysteine-rich 61 (Cyr61/CCN1) is a member of the CCN family of matrix cell proteins and have been reported to be abundant in the secretome of repair mediating SCs. In this study we investigate the function of Cyr61 in SCs. Results We observed Cyr61 was expressed both in vivo and in vitro. The promoting effect of Cyr61 on SC proliferation and migration was through autocrine and paracrine mechanisms. SCs expressed αvβ3 integrin and the effect of Cyr61 on SC proliferation and migration could be blocked via αvβ3 integrin. Cyr61 could influence c-Jun protein expression in cultured SCs. Conclusions In this study, we found that Cyr61 promotes SC proliferation and migration via αvβ3 integrin and regulates c-Jun expression. Our study contributes to the understanding of cellular and molecular mechanisms underlying SC’s function during nerve injury, and thus, may facilitate the regeneration of peripheral nerves after injury.

scholarly journals TRIM27 interacts with Iκbα to promote the growth of human renal cancer cells through regulating the NF-κB pathway

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chengwu Xiao ◽  
Wei Zhang ◽  
Meimian Hua ◽  
Huan Chen ◽  
Bin Yang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Mrna Levels ◽  
Loss Of Function ◽  
Protein Levels ◽  
Kaplan Meier ◽  
Cancer Genome Atlas

Abstract Background The tripartite motif (TRIM) family proteins exhibit oncogenic roles in various cancers. The roles of TRIM27, a member of the TRIM super family, in renal cell carcinoma (RCC) remained unexplored. In the current study, we aimed to investigate the clinical impact and roles of TRIM27 in the development of RCC. Methods The mRNA levels of TRIM27 and Kaplan–Meier survival of RCC were analyzed from The Cancer Genome Atlas database. Real-time PCR and Western blotting were used to measure the mRNA and protein levels of TRIM27 both in vivo and in vitro. siRNA and TRIM27 were exogenously overexpressed in RCC cell lines to manipulate TRIM27 expression. Results We discovered that TRIM27 was elevated in RCC patients, and the expression of TRIM27 was closely correlated with poor prognosis. The loss of function and gain of function results illustrated that TRIM27 promotes cell proliferation and inhibits apoptosis in RCC cell lines. Furthermore, TRIM27 expression was positively associated with NF-κB expression in patients with RCC. Blocking the activity of NF-κB attenuated the TRIM27-mediated enhancement of proliferation and inhibition of apoptosis. TRIM27 directly interacted with Iκbα, an inhibitor of NF-κB, to promote its ubiquitination, and the inhibitory effects of TRIM27 on Iκbα led to NF-κB activation. Conclusions Our results suggest that TRIM27 exhibits an oncogenic role in RCC by regulating NF-κB signaling. TRIM27 serves as a specific prognostic indicator for RCC, and strategies targeting the suppression of TRIM27 function may shed light on future therapeutic approaches.

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.

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