scholarly journals USP1 Promotes GC Metastasis via Stabilizing ID2

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Nuoya Li ◽  
Lei Wu ◽  
Xingye Zuo ◽  
Huilong Luo ◽  
Yanling Sheng ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Survival Rates ◽  
Underlying Mechanism ◽  
Poor Survival ◽  
Cellular Analysis ◽  
Potential Biomarker ◽  
Therapy Target

Gastric cancer (GC) is one of the most common malignant tumors all over the world. And recurrence and metastasis are still the main causes of low survival rate for advanced GC. USP1 has been shown overexpressed in multiple cancers, which indicate its important biomarker in tumorigenesis and development. Our study is aimed at defining the exact role of USP1 on GC metastasis and the underlying mechanism. USP1 was firstly found overexpressed in GC tissues and relatively high-expression levels conferred poor survival rates. Then, real-time cellular analysis (RTCA) showed that USP1 knockdown inhibited GC metastasis both in vitro and in vivo. Mechanically, we demonstrated that USP1 promoted GC metastasis via upregulating ID2 expression and further confirmed that USP1 stabilized ID2 expression through deubiquitinating ID2 in GC. In conclusion, our study showed that USP1 promoted GC metastasis via stabilizing ID2 expression, which provides a potential biomarker and therapy target for GC.

scholarly journals LncRNA SNHG11 Promotes Temozolomide Resistance in Glioblastoma via Promoting MGMT Expression

2021 ◽  
Author(s):  
Tao Ji ◽  
Xiao Lyu ◽  
Yongping You
Keyword(s):  
Rna Binding ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Promoter Regions ◽  
Mgmt Expression ◽  
Potential Biomarker ◽  
Rip Assay

Abstract Background Acquired TMZ resistance is considered as the main reason for the poor prognosis of glioblastoma (GBM) patients. However, underlying mechanism remains unknown. Long noncoding RNAs (lncRNAs) have emerged as important regulators in multiple biological processes. Methods SNHG11 expression in cells and GBM tissues was measured using qRT-PCR. In vitro studies, including CCK-8, colony formation assay, flow cytometry and western blot, were employed to measure the role of SNHG11. Interaction between miR-7-5p, SNHG11, and IRS2 was examined by dual luciferase reporter assay, as well as RNA binding protein immunoprecipitation (RIP) assay. CHIP assays were used to measure the role of SNHG11/miR-7-5p/IRS2 axis on modulating the H3K9 acetylation of MGMT. Results SNHG11 overexpression in GBM tissues contributes to TMZ resistance. In vitro and in vivo studies confirmed that SNHG11 promoted TMZ resistance in GBM cells. In addition, SNHG11 conferred TMZ resistance through increasing MGMT expression. Furthermore, SNHG11 could function as ceRNA by sponging miR-7-5p, which led to increased IRS2 expression. SNHG11/miR-7-5p/IRS2 axis increased MGMT expression by promoting the acetylation of H3K9 in MGMT promoter regions. Conclusion Taken together, our results revealed that targeting SNHG11 is a potential therapy to overcome TMZ resistance. And SNHG11 in GBM tissues is a potential biomarker for predicting response to TMZ.

scholarly journals lncRNA CASC19 Contributes to Radioresistance of Nasopharyngeal Carcinoma by Promoting Autophagy via AMPK-mTOR Pathway

2021 ◽  
Vol 22 (3) ◽  
pp. 1407
Author(s):  
Hongxia Liu ◽  
Wang Zheng ◽  
Qianping Chen ◽  
Yuchuan Zhou ◽  
Yan Pan ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cell Line ◽  
Malignant Tumors ◽  
Underlying Mechanism ◽  
Mtor Pathway ◽  
Rna Seq ◽  
Cellular Autophagy ◽  
First Time

Nasopharyngeal carcinoma (NPC) is one of the most frequent head and neck malignant tumors and is majorly treated by radiotherapy. However, radiation resistance remains a serious obstacle to the successful treatment of NPC. The aim of this study was to discover the underlying mechanism of radioresistance and to elucidate novel genes that may play important roles in the regulation of NPC radiosensitivity. By using RNA-seq analysis of NPC cell line CNE2 and its radioresistant cell line CNE2R, lncRNA CASC19 was screened out as a candidate radioresistance marker. Both in vitro and in vivo data demonstrated that a high expression level of CASC19 was positively correlated with the radioresistance of NPC, and the radiosensitivity of NPC cells was considerably enhanced by knockdown of CASC19. The incidence of autophagy was enhanced in CNE2R in comparison with CNE2 and another NPC cell line HONE1, and silencing autophagy with LC3 siRNA (siLC3) sensitized NPC cells to irradiation. Furthermore, CASC19 siRNA (siCASC19) suppressed cellular autophagy by inhibiting the AMPK/mTOR pathway and promoted apoptosis through the PARP1 pathway. Our results revealed for the first time that lncRNA CASC19 contributed to the radioresistance of NPC by regulating autophagy. In significance, CASC19 might be a potential molecular biomarker and a new therapeutic target in NPC.

Identification of long non-coding RNA HERC2P2 as a tumor suppressor in glioma

2019 ◽  
Vol 40 (8) ◽  
pp. 956-964 ◽  
Author(s):  
Chao Yang ◽  
Lin Wang ◽  
Jia Sun ◽  
Jun-hu Zhou ◽  
Yan-li Tan ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Survival Rates ◽  
Hect Domain ◽  
Cerna Network ◽  
Non Coding Rna ◽  
Potential Biomarker ◽  
Scratch Tests ◽  
Long Non Coding Rna

Abstract Long non-coding RNAs (lncRNAs) have been reported to play important roles in glioma; however, most of them promote glioma progression. We constructed a competing endogenous (ceRNA) network based on the Chinese Glioma Genome Atlas dataset, and lncRNA hect domain and RLD 2 pseudogene 2 (HERC2P2) is the core of this network. Highly connected genes in the ceRNA network classified the glioma patients into three clusters with significantly different survival rates. The expression of HERC2P2 is positively correlated with survival and negatively correlated with clinical grade. Cell colony formation, Transwell and cell scratch tests were performed to evaluate the role of HERC2P2 in glioblastoma growth. Furthermore, we overexpressed HERC2P2 in U87 cells and established a mouse intracranial glioma model to examine the function of HERC2P2 in vivo. In conclusion, we identified a lncRNA with tumor suppressor functions in glioma that could be a potential biomarker for glioma patients.

scholarly journals Citrulline directly modulates muscle protein synthesis via the PI3K/MAPK/4E-BP1 pathway in a malnourished state: evidence from in vivo, ex vivo, and in vitro studies

2017 ◽  
Vol 312 (1) ◽  
pp. E27-E36 ◽  
Author(s):  
Servane Le Plénier ◽  
Arthur Goron ◽  
Athanassia Sotiropoulos ◽  
Eliane Archambault ◽  
Chantal Guihenneuc ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Ex Vivo ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Fold Increase ◽  
Underlying Mechanism ◽  
Muscle Homeostasis

Citrulline (CIT) is an endogenous amino acid produced by the intestine. Recent literature has consistently shown CIT to be an activator of muscle protein synthesis (MPS). However, the underlying mechanism is still unknown. Our working hypothesis was that CIT might regulate muscle homeostasis directly through the mTORC1/PI3K/MAPK pathways. Because CIT undergoes both interorgan and intraorgan trafficking and metabolism, we combined three approaches: in vivo, ex vivo, and in vitro. Using a model of malnourished aged rats, CIT supplementation activated the phosphorylation of S6K1 and 4E-BP1 in muscle. Interestingly, the increase in S6K1 phosphorylation was positively correlated ( P < 0.05) with plasma CIT concentration. In a model of isolated incubated skeletal muscle from malnourished rats, CIT enhanced MPS (from 30 to 80% CIT vs. Ctrl, P < 0.05), and the CIT effect was abolished in the presence of wortmannin, rapamycin, and PD-98059. In vitro, on myotubes in culture, CIT led to a 2.5-fold increase in S6K1 phosphorylation and a 1.5-fold increase in 4E-BP1 phosphorylation. Both rapamycin and PD-98059 inhibited the CIT effect on S6K1, whereas only LY-294002 inhibited the CIT effect on both S6K1 and 4E-BP1. These findings show that CIT is a signaling agent for muscle homeostasis, suggesting a new role of the intestine in muscle mass control.

EDD1 predicts prognosis and regulates gastric cancer growth in vitro and in vivo via miR-22

2016 ◽  
Vol 0 (0) ◽  
Author(s):  
Min Yang ◽  
Nan Jiang ◽  
Qi-wei Cao ◽  
Qing Sun
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Patient Survival ◽  
Underlying Mechanism ◽  
Gastric Cancer Cells ◽  
Cancer Tissues

Abstract Gastric cancer is the most common digestive malignant tumor worldwild. EDD1 was reported to be frequently amplified in several tumors and played an important role in the tumorigenesis process. However, the biological role and potential mechanism of EDD1 in gastric cancer remains poorly understood. In this study, we are aim to investigate the effect of EDD1 on gastric cancer progression and to explore the underlying mechanism. The results showed the significant up-regulation of EDD1 in -gastric cancer cell tissues and lines. The expression level of EDD1 was also positively associated with advanced clinical stages and predicted poor overall patient survival and poor disease-free patient survival. Besides, EDD1 knockdown markedly inhibited cell viability, colony formation, and suppressed tumor growth. Opposite results were obtained in gastric cancer cells with EDD1 overexpression. EDD1 knockdown was also found to induce gastric cancer cells apoptosis. Further investigation indicated that the oncogenic role of EDD1 in regulating gastric cancer cells growth and apoptosis was related to its PABC domain and directly through targeting miR-22, which was significantly down-regulated in gastric cancer tissues. Totally, our study suggests that EDD1 plays an oncogenic role in gastric cancer and may be a potential therapeutic target for gastric cancer.

scholarly journals Melatonin Relieves Busulfan-Induced Spermatogonial Stem Cell Apoptosis of Mouse Testis by Inhibiting Endoplasmic Reticulum Stress

2017 ◽  
Vol 44 (6) ◽  
pp. 2407-2421 ◽  
Author(s):  
Yanhua Cui ◽  
Lipeng Ren ◽  
Bo Li ◽  
Jia Fang ◽  
Yuanxin Zhai ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Caspase 3 ◽  
Survival Rates ◽  
Underlying Mechanism ◽  
Pcr Analysis ◽  
Caspase 12 ◽  
Apoptosis Proteins

Background/Aims: Busulfan is commonly used for cancer chemotherapy. Although it has the advantage of increasing the survival rate of patients, it can cause male infertility via damaging the testes and reducing sperm counts. Therefore, the underlying mechanism should be explored, and new agents should be developed to protect the male reproductive system from busulfan-induced damage. Endoplasmic reticulum stress (ERS) is considered a key contributor to numerous pathologies. Despite several studies linking ERS to toxicants, studies have yet to determine whether ERS is a contributing factor to busulfan-induced testicular damage. Melatonin is a well-known broad-spectrum antioxidant, anti-inflammatory and antitumour agent, but the effects of melatonin on busulfan-induced ERS in mouse testes damage are less documented. Methods: The effects of melatonin were measured by immunofluorescence staining, Western blot, qRT-PCR analysis and flow cytometry assay. The underlying mechanism was investigated by measuring ERS. Results: We found that ERS was strongly activated in mouse testes (in vivo) and the C18-4 cell line (in vitro) after busulfan administration. ERS-related apoptosis proteins such as caspase-12, CHOP and caspase-3 were activated, and the expression of apoptotic proteins such as P53 and PUMA were upregulated. Furthermore, we investigated whether melatonin reduced the extent of damage to mouse testes and improved the survival rates of busulfan-treated mice. When exploring the underlying mechanisms, we found melatonin could counteract ERS by decreasing the expression levels of the ERS markers GRP78, ATF6, pIRE1 and XBP1 in mouse testes and mouse SSCs (C18-4 cells). Moreover, it blocked the activation of ERS-related apoptosis proteins caspase-12, CHOP and caspase-3 and suppressed P53 and PUMA expression stimulated by busulfan both in vivo and in vitro. Conclusion: Our results demonstrate that ERS is an important mediator for busulfan-induced apoptosis. The attenuation of ERS by melatonin can prevent busulfan-treated SSCs apoptosis and protect busulfan-treated testes from damage. Thus, this study suggests that melatonin may alleviate the side effects of busulfan for male patients during clinical treatment.

scholarly journals DCTPP1, an Oncogene Regulated by miR-378a-3p, Promotes Proliferation of Breast Cancer via DNA Repair Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Ming Niu ◽  
Ming Shan ◽  
Yang Liu ◽  
Yanni Song ◽  
Ji-guang Han ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Dna Repair ◽  
Survival Rates ◽  
The Other ◽  
Poor Survival ◽  
Induced Apoptosis ◽  
Cell Growth And Proliferation

Breast cancer (BRCA) is one of the most deadly cancers worldwide, with poor survival rates that could be due to its high proliferation. Human all-alpha dCTP pyrophosphatase 1 (DCTPP1) is implicated in numerous diseases, including cancers. However, its role in BRCA is unclear. In this study, we used bioinformatic analyses of the ONCOMINE, UALCAN, and GEPIA databases to determine the expression pattern of DCTPP1 in BRCA. We found that elevated DCTPP1 levels correlate with poor BRCA prognosis. DCTPP1 silencing inhibited BRCA cell proliferation and induced apoptosis in vitro, as well as in vivo. Our data show that this tumorigenic effect depends on DNA repair signaling. Moreover, we found that DCTPP1 is directly modulated by miR-378a-3p, whose downregulation is linked to BRCA progression. Our results showed down-regulation of miR-378a-3p in BRCA. Upregulation of miR-378a-3p, on the other hand, can inhibit BRCA cell growth and proliferation. This study shows that reduced miR-378a-3p level enhances DCTPP1 expression in BRCA, which promotes proliferation by activating DNA repair signaling in BRCA.

scholarly journals Nujiangexanthone A Inhibits Hepatocellular Carcinoma Metastasis via Down Regulation of Cofilin 1

2021 ◽  
Vol 9 ◽  
Author(s):  
Li Zhang ◽  
Zongtao Chai ◽  
Siyuan Kong ◽  
Jiling Feng ◽  
Man Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Malignant Tumors ◽  
Disease Free Survival ◽  
Mechanism Study ◽  
Down Regulation ◽  
Free Survival ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) is one of the malignant tumors with poor prognosis. High expression level of cofilin 1 (CFL1) has been found in many types of cancers. However, the role of CFL1 in HCC hasn’t been known clearly. Here, we found that CFL1 was up regulated in human HCC and significantly associated with both overall survival and disease-free survival in HCC patients. Nujiangexanthone A (NJXA), the caged xanthones, isolated from gamboge plants decreased the expression of CFL1, which also inhibited the migration, invasion and metastasis of HCC cells in vitro and in vivo. Down regulation of CFL1 inhibited aggressiveness of HCC cells, which mimicked the effect of NJXA. Mechanism study indicated that, knockdown of CFL1 or treatment with NJXA increased the level of F-actin and disturbed the balance between F-actin and G-actin. In conclusion, our findings reveal the role of CFL1 in HCC metastasis through the CFL1/F-actin axis, and suggest that CFL1 may be a potential prognostic marker and a new therapeutic target. NJXA can effectively inhibit the metastasis of HCC cells by down regulating the expression of CFL1, which indicates the potential of NJXA for preventing metastasis in HCC.

scholarly journals Inhibiting IL-6 During Cytokine Storm in COVID-19: Potential Role of Natural Products

2021 ◽  
Author(s):  
Amirreza Nasirzadeh ◽  
Mohammad hosein Jafarzadeh Maivan ◽  
Javad Bazeli ◽  
Jafar Hajavi ◽  
Negar Yavarmanesh ◽  
...  
Keyword(s):  
Natural Products ◽  
Medicinal Plants ◽  
Inflammatory Responses ◽  
Survival Rates ◽  
Inhibitory Effect ◽  
Cytokine Storm ◽  
Regulatory Effects

Plant species with anti-inflammatory properties might play an essential role in combatting COVID-19 via reducing cytokine storms. We aimed to review the extant evidence of the potential therapeutic efficacy of natural products against cytokine storms by inhibiting interleukin-6 (IL-6) as a major pathological mediator. Data were collected following an electronic search in major databases (Pubmed, Scopus, Web of Science, Google Scholar) and also preprint articles on preprint and medRxiv servers by using a combination of relevant keywords. Seventeen active compounds and medicinal plants were found and reviewed in the present review. Results of both in-vivo and in-vitro experiments conducted on these compounds showed that Phillyrin, SMFM, Qiangzhi decoction, curcumin, Shen-Fu, Forsythia, and Alpha-Mangostin inhibit the production of IL-6. Andrographolide and Liu Shen Wan have an inhibitory effect on releasing this agent, while Ilex Asprella and Deoxy-11,12-didehydroandrographolide and naringin reduce the expression of IL-6. Theaflavin and Cholorogenic acid inhibit the secretion of IL-6, Xuebijing, and Chai-Hu-Gui-Zi-Gan-Jiang-Tang and Lipanpaidu prescription can reduce the serum level of IL-6. These agents also effectively improve infected lungs, increase survival rates, and minimize tissue damage. Medicinal plants and their phytochemical ingredients with down-regulatory effects on the expression of IL-6 have a potential influence on the inhibition of cytokine storms during viral infection caused by COVID-19. Therefore, phytochemicals could be regarded as promising candidates for managing cytokine storm inflammatory responses due to COVID-19 infection.

scholarly journals MTA2 as a Potential Biomarker and Its Involvement in Metastatic Progression of Human Renal Cancer by miR-133b Targeting MMP-9

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1851 ◽  
Author(s):  
Yong-Syuan Chen ◽  
Tung-Wei Hung ◽  
Shih-Chi Su ◽  
Chia-Liang Lin ◽  
Shun-Fa Yang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Survival Rates ◽  
The Cancer Genome Atlas ◽  
Metastatic Progression ◽  
Tumour Grade ◽  
Potential Biomarker ◽  
Cancer Genome Atlas ◽  
Metalloproteinase 9

Metastasis-associated protein 2 (MTA2) was previously known as a requirement to maintain malignant potentials in several human cancers. However, the role of MTA2 in the progression of renal cell carcinoma (RCC) has not yet been delineated. In this study, MTA2 expression was significantly increased in RCC tissues and cell lines. Increased MTA2 expression was significantly associated with tumour grade (p = 0.002) and was an independent prognostic factor for overall survival with a high RCC tumour grade. MTA2 knockdown inhibited the migration, invasion, and in vivo metastasis of RCC cells without effects on cell proliferation. Regarding molecular mechanisms, MTA2 knockdown reduced the activity, protein level, and mRNA expression of matrix metalloproteinase-9 (MMP-9) in RCC cells. Further analyses demonstrated that patients with lower miR-133b expression had poorer survival rates than those with higher expression from The Cancer Genome Atlas database. Moreover, miR-133b modulated the 3′untranslated region (UTR) of MMP-9 promoter activities and subsequently the migratory and invasive abilities of these dysregulated expressions of MTA2 in RCC cells. The inhibition of MTA2 could contribute to human RCC metastasis by regulating the expression of miR-133b targeting MMP-9 expression.

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