Supplementary Figure 3 from Dimethyl Fumarate Controls the NRF2/DJ-1 Axis in Cancer Cells: Therapeutic Applications
Nathaniel Edward Bennett SaiduGaëlle NoéOlivier CerlesLuc CabelNiloufar Kavian-TesslerSandrine ChouzenouxMathilde BahuaudChristiane ChéreauCarole NiccoKaren LeroyBruno BorgheseFrançois GoldwasserFrédéric BatteuxJérôme Alexandre
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<p>Concentration-dependant cellular effects of DMF in OVCAR3 cells.</p>MicroRNA-1292-5p inhibits cell growth, migration and invasion of gastric carcinoma by targeting DEK.
Gastric cancer ranks as the third most lethal cancer worldwide. Although many efforts have been made to identify novel markers for early diagnosis and effective drugs for the treatment of gastric cancer, the outcome is still poor due to delayed diagnosis and lack of therapeutic options. MicroRNAs (miRNAs) play crucial roles during tumorigenesis, and several miRNAs were found to be critical for gastric cancer development, offering promise as therapeutic targets. The results of this study indicate that a novel miRNA, miR-1292-5p, is downregulated both in gastric carcinoma in vivo and in gastric cancer cell lines in vitro. In addition, we showed that attenuation of miR-1292-5p inhibited the growth, migration and invasion of the AGS and SGC-7901 gastric cancer cell lines. Importantly, our results demonstrate that the proto-oncogenic protein DEK is a direct target of miR-1292-5p in gastric carcinoma. Our results therefore demonstrate a tumor suppressor role of miR-1292-5p in gastric carcinoma and hint at the diagnostic and therapeutic potential of the miR-1292-5p/DEK pathway in gastric cancer.
Gastric carcinoma
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Gastric cancer is one of the most common malignancies of the digestive system with high mortality rates. Recent studies have demonstrated that circRNAs are novel noncoding RNAs that play vital roles in the tumorigenesis and development of gastric cancer. Our study found a novel circRNA, namely, hsa_circ_0107595 (also called circABCA5), that is overexpressed in gastric cancer based on circRNA sequencing. qPCR demonstrated its overexpression in gastric cancer specimens. The overexpression or knockdown of circABCA5 in gastric cancer cell lines was achieved by lentiviral-mediated transfection. All MTS, EdU, Transwell and migration assays and xenograft experiments demonstrated that circABCA5 could promote gastric cancer proliferation, invasion, and migration in vitro and in vivo. Mechanistically, both RIP and RNA pulldown assays confirmed that circABCA5 could bind to the SPI1 protein, upregulate SPI1 expression, and promote its nuclear translocation. SPI1 could further promote the malignant phenotype of gastric cancer by activating IL6/JAK2/STAT3 signaling. In addition, EIF4A3 could directly bind to circABCA5, promoting its stability and expression. Our study reveals that circABCA5 plays a vital role in the diagnosis and prognosis of gastric cancer and may even be developed as a molecular target for the treatment of gastric cancer.
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MicroRNA has been recently recognized as playing a prominent role in tumorigenesis and metastasis. Here, we report that miR-338-3p was epigenetically silenced in gastric cancer, and its down-regulation was significantly correlated with gastric cancer clinicopathological features. Strikingly, restoring miR-338-3p expression in SGC-7901 gastric cancer cells inhibited proliferation, migration, invasion and tumorigenicity in vitro and in vivo, at least partly through inducing apoptosis. Furthermore, we demonstrate the oncogene SSX2IP is a target of miR-338-3p. We propose that miR-338-3p functions as a tumor suppressor in gastric cancer, and the methylation status of its CpG island could serve as a potential diagnostic marker for gastric cancer.
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Results from recent studies suggest that aberrant microRNA expression is common in numerous cancers. Although miR-338-3p has been implicated in hepatocellular carcinoma, its role in gastric cancer is unknown. To this end, we report that miR-338-3p is downregulated in both gastric cancer tissue and cell lines. Forced expression of miR-338-3p inhibited cell proliferation and clonogenicity and induced a G1-S arrest as well as apoptosis in gastric cancer cells. Furthermore, P-Rex2a (PREX2) was identified as a direct target of miR-338-3p, and silencing P-Rex2a resulted in the same biologic effects of miR-338-3p expression in gastric cancer cells. Furthermore, both enforced expression of miR-338-3p or silencing of P-Rex2a resulted in activation of PTEN, leading to a decline in AKT phosphorylation. Also, miR-338-3p markedly inhibited the in vivo tumorigenicity in a nude mouse xenograft model system. These results demonstrate that miR-338-3p affects gastric cancer progression through PTEN-AKT signaling by targeting P-Rex2a in gastric cancer cells, which posits miR-338-3p as a novel strategy for gastric cancer treatment.miR-338-3p acts as a novel tumor suppressor that blocks the growth of gastric cancer cells through PTEN-PI3K signaling by targeting P-Rex2a.
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Gastric cancer is the fourth most common cancer and the second most frequent cause of cancer‑associated mortality in the world. Previous studies have revealed that expression levels of microRNAs (miRNAs) are associated with the initiation and progression of several types of cancer, including gastric cancer. Previous studies have demonstrated that the abnormal expression of miRNA‑136 may serve a function in the progression of several types of human cancer. However, the expression pattern of miR‑136, its functions and underlying molecular mechanisms in gastric cancer remain unresolved. In the present study, it was revealed that the expression of miR‑136 was aberrantly up regulated in gastric cancer tissues and cell lines. The suppression of miR‑136 was able to inhibit proliferation and invasion in gastric cancer cell lines. Furthermore, phosphatase and tensin homolog (PTEN) was identified as a direct target gene of miR‑136 in gastric cancer. PTEN was under expressed in gastric cancer tissues compared with non‑tumor gastric tissues, and PTEN expression was negatively correlated with miR‑136 expression. Furthermore, PTEN overexpression mimics the effects of miR‑136 knockdown on gastric cancer cells. Additionally, miR‑136 under expression decreased phospho‑(p) AKT expression, but did not affect AKT expression in gastric cancer cells. In conclusion, the data of the present study suggest that miR‑136 acts as an oncogene in gastric cancer via regulation of the PTEN/AKT/p‑AKT signaling pathway and may potentially serve as a novel therapeutic target for the treatment of gastric cancer.
Tensin
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Poor prognosis of gastric cancer is related to not only malignancy of gastric cancer cells, but also the tumor microenvironment. Thus drugs, which can inhibit both of them, are urgently needed to be explored. Studies on effect of Proton-pump inhibitors (PPIs) in anti-neoplasms are increasing, but is rare in gastric in gastric cancer. Here we investigated how the gastric cancer microenvironment is regulated by PPIs. The objective response rate of gastric cancer patients in our hospital treated by PPIs is investigated. PPIs' effects were further explored by observing the change of microRNAs, cytokines, cellular apoptosis. Bioinformatic pathway analysis of microarray was used to discover the pathway involved in PPIs' regulation of gastric cancer microenvironments. Immunoblotting assays and qRT-PCR were used to define molecular events with PPIs treatment. We report here that PPIs can improve the prognosis of advanced gastric cancer patients; and inhibit the progress of gastric cancer both in vivo and in vitro. Moreover, high dose of PPIs can regulate the pathway associated with tumor malignancy and microenvironment via inhibiting the release of exosomes, which packed microRNAs. PPIs can inhibit the transformation of CAFs (cancer associated fibroblasts) and cytokines released from CAFs. In addition, PPIs inhibit the malignancy of gastric cancer through regulating HIF-1α-FOXO1 axis. High dose of PPIs can inhibit malignancy of gastric cancer and regulate its surrounding tumor microenvironment. This finding suggests that PPIs maybe of potential value as a therapeutic tool for treatment of gastric cancer.
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CXC chemokine receptor 7 (CXCR7) is highly expressed in various type of cancers and promotes cancer progression and metastasis. However, the biological role and regulation of CXCR7 in gastric cancer remains unclear, and little is known about compounds that modulate CXCR7. Here, we investigated the role of CXCR7 in gastric tumorigenesis, and the effects of decursin, which is derived from Angelica gigas Nakai, on CXCR7. Our results showed that CXCR7 significantly promoted growth of gastric cancer cells and increased migration and invasion, which was mediated by the STAT3/c-Myc pathway. We also confirmed that decursin had an antitumor effect through down-regulating the expression of CXCR7 in gastric cancer. Furthermore, apoptotic cell death was induced through the reduction of anti-apoptotic factors such as Bcl-2 in vitro and in vivo. Our findings show that CXCR7 in gastric cancer promotes cancer progression through the STAT3/c-Myc pathway and that decursin is a natural compound that may target CXCR7 in gastric cancer treatment.
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Бұл зерттеужұмысындaКaно моделітурaлы жәнеоғaн қaтыстытолықмәліметберілгенжәнеуниверситетстуденттерінебaғыттaлғaн қолдaнбaлы (кейстік)зерттеужүргізілген.АхметЯссaуи университетініңстуденттеріүшін Кaно моделіқолдaнылғaн, олaрдың жоғaры білімберусaпaсынa қоятынмaңыздытaлaптaры, яғнисaпaлық қaжеттіліктері,олaрдың мaңыздылығытурaлы жәнесaпaлық қaжеттіліктерінеқaтыстыөз университетінқaлaй бaғaлaйтындығытурaлы сұрaқтaр қойылғaн. Осы зерттеудіңмaқсaты АхметЯсaуи университетіндетуризмменеджментіжәнеқaржы бaкaлaвриaт бaғдaрлaмaлaрыныңсaпaсынa қaтыстыстуденттердіңқaжеттіліктерінaнықтaу, студенттердіңқaнaғaттaну, қaнaғaттaнбaу дәрежелерінбелгілеу,білімберусaпaсын aнықтaу мен жетілдіружолдaрын тaлдaу болыптaбылaды. Осы мaқсaтқaжетуүшін, ең aлдыменКaно сaуaлнaмaсы түзіліп,116 студенткеқолдaнылдыжәнебілімберугежәнеоның сaпaсынa қaтыстыстуденттердіңтaлaптaры мен қaжеттіліктерітоптықжұмыстaрaрқылыaнықтaлды. Екіншіден,бұл aнықтaлғaн тaлaптaр мен қaжеттіліктерКaно бaғaлaу кестесіменжіктелді.Осылaйшa, сaпa тaлaптaры төрт сaнaтқa бөлінді:болуытиіс, бір өлшемді,тaртымдыжәнебейтaрaп.Соңындa,қaнaғaттaну мен қaнaғaттaнбaудың мәндеріесептелдіжәнестуденттердіңқaнaғaттaну мен қaнaғaттaнбaу деңгейлерінжоғaрылaту мен төмендетудеосытaлaптaр мен қaжеттіліктердіңрөліaйқын aнықтaлды.Түйінсөздер:сaпa, сaпaлық қaжеттіліктер,білімберусaпaсы, Кaно моделі.
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The nationally-recognized Susquehanna
Chorale will delight audiences of all
ages with a diverse mix of classic and
contemporary pieces. The ChoraleAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂA¢AÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂs
performances have been described
as AÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂA¢AÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂemotionally unfiltered, honest
music making, successful in their
aim to make the audience feel,
to be moved, to be part of the
performance - and all this while
working at an extremely high
musical level.AÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂA¢AÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂA Experience choral
singing that will take you to new
heights!
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Growing evidence has indicated that the long noncoding RNA (lncRNA) CYTOR is involved in the initiation and progression of malignancies, including gastric cancer. Nevertheless, the mechanisms of CYTOR in gastric cancer development are not fully understood. In the present study, we aimed to clarify the association of CYTOR, miR-103, and RAB10 in gastric cancer progression. We found that CYTOR expression was increased in metastatic gastric cancer biopsies compared with that in primary samples. CYTOR expression was significantly positively correlated with the invasiveness, lymph node metastasis, and advanced stages of gastric cancer. In addition, downregulation of CYTOR expression hampered cell proliferation and migration but induced cell apoptosis. Furthermore, CYTOR sponged miR-103 and diminished miR-103 expression, thus rescuing oncogene RAB10 expression. Knockdown of CYTOR suppressed tumor growth in human BGC823 mouse models. These findings suggest that the CYTOR/miR-103/RAB10 axis is a novel signaling pathway that facilitates gastric cancer progression. CYTOR-targeted interventions provide a rationale to improve therapies targeting gastric cancer progression.
Tumor progression
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