scholarly journals LncRNA PVT1 Mediates Antiapoptosis and 5-Fluorouracil Resistance via Increasing Bcl2 Expression in Gastric Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Peizhun Du ◽  
Cheng’en Hu ◽  
Yunyun Qin ◽  
Jing Zhao ◽  
Rajan Patel ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Treatment Resistance ◽  
Cell Viability Assay ◽  
Western Blot Assay ◽  
Viability Assay ◽  
Kaplan Meier ◽  
Relative Gene ◽  
Variant Translocation

Purpose. Plasmacytoma variant translocation 1 (PVT1) is a long noncoding RNA encoded by the human PVT1 gene, which has been verified to mediate tumorigenesis in gastric cancer. However, the underlying molecular mechanisms of PVT1 in gastric cancer (GC) remain largely unknown. Methods. The tumorigenic ability of PVT1 was verified by subcutaneous and orthotopic mouse models. Flow cytometry assay and TdT-mediated dUTP Nick-End Labeling staining were conducted to explore the effects of PVT1 on gastric cancer cell apoptosis. We investigated the relative gene and protein that are involved in apoptosis in real-time PCR and western blot assay. The resistance to 5- Fluorouracil (5-Fu) caused by PVT1 was evaluated using cell viability assay. Then, to confirm the effects of PVT1 on 5-Fu resistance, we conducted the Kaplan-Meier analysis based on three public databases. Results. We confirmed that PVT1 can promote the progression of gastric cancer. PVT1 inhibited the apoptosis of GC cells, which may account for its promotion on GC. We confirmed that PVT1 can regulate the expression of Bcl2 and enhance drug-resistance of gastric cancer to 5-Fu. Kaplan-Meier analysis showed that patients with high PVT1 expression do not experience survival related benefits from 5-Fu based chemotherapy; instead, therapy containing no 5-Fu chemotherapy can improve the first progression survival and overall survival of high PVT1 expression GC patients significantly. Conclusion. Our results showed that PVT1 can inhibit the apoptosis and enhance the 5-Fu resistance of gastric cancer through the activation of Bcl2. PVT1 has the potential to serve as an indicator to predict 5-Fu treatment resistance.

scholarly journals Identification of dysregulated long noncoding RNA and associated mechanism in gastric cancer

2020 ◽  
Author(s):  
Liang Shao ◽  
Yanan Ming ◽  
Zhaoming Zhou
Keyword(s):  
Gastric Cancer ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Cell Metabolism ◽  
Meta Analysis ◽  
Venn Diagram ◽  
Interactive Analysis ◽  
Kaplan Meier ◽  
Diagnostic Potential ◽  
Crucial Component

Abstract Gastric cancer (GC) is one of the most malignant epithelial tumors. The incidence of GC varies worldwide, and nearly half of the cases occur in Asian countries, especially in Japan and China. GC is the second leading cause of cancer-related deaths in the world, and current prognosis of advanced GC remains dismal despite improvements in diagnosis and therapy. Our current study aimed to identify significant long noncoding RNAs (lncRNAs) that could be used for prognosis and for the elucidation of associated molecular mechanisms. This study identified a substantial variety of reports using high-throughput lncRNA detection to investigate the expression of lncRNAs in GC development. However, the reported potentially diagnostic lncRNAs were unsuitable for meta-analysis, so we verified the expression of diagnostic lncRNAs and selected eight of them using Gene Expression Profiling Interactive Analysis (GEPIA). Next, we explored interactions of selected lncRNAs using Qiagen’s IPA system. We also identified differentially expressed genes (DEGs) of GC using the GEO2R online tool and datasets GSE52149, GSE19826, and GSE79973. To reveal genes that could be regulated by the selected lncRNA in GC, we used a Venn diagram and selected IGF2BP3 and FOLR1 as potential downstream targets of lncRNAs H19 and PVT1, respectively. Expression of IGF2BP3 and FOLR1 in GC validated by GEPIA was related to the worse prognosis for GC patients as shown by Kaplan Meier plots. Considering that IGF2BP3 promotes the expression of H19 and PEG10, down-regulation of their expression may improve the prognosis for GC patients, although at this time there is no evidence for direct involvement of IGF2BP3 in the regulation of these lncRNAs. The second DEG, FOLR1, is a crucial component of cell metabolism and DNA synthesis/repair required for cancer cell division. However, the role of FOLR1 in the etiology and progression of GC requires further study. In conclusion, using an integrated bioinformatic approach we identified eight significantly altered lncRNAs with diagnostic potential in GC patients. We also identified two axes - H19-IGF2BP3 and PVT1-FOLR1 – that may be related to the prognosis of GC and provide new insights into the etiology of GC and management of GC patients.

scholarly journals Growth hormone protects against radiotherapy-induced cell death

2002 ◽  
pp. 535-541 ◽  
Author(s):  
O Madrid ◽  
S Varea ◽  
I Sanchez-Perez ◽  
L Gomez-Garcia ◽  
E De Miguel ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Cell Death ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Molecular Mechanisms ◽  
Dna Double Strand Breaks ◽  
Cell Viability Assay ◽  
Viability Assay ◽  
Rat Growth

BACKGROUND: In vivo treatment with growth hormone reduces radiation-associated mortality. The molecular mechanisms underlying this effect are unknown. It has been described that increased sensitivity to ionising radiation can be due to defects in machinery involved in detection and/or repair of DNA double-strand breaks. OBJECTIVE: To study the mechanisms involved in growth hormone action on the increased survival in irradiated cells. MATERIALS AND METHODS: CHO-4 cells stably expressing the growth hormone receptor were used. A cell viability assay was carried out to analyse the increase in survival induced by growth hormone in irradiated cells. To investigate whether the DNA repair mechanism could be implicated in this effect we performed DNA reactivation assays using pHIV-LUC and pCMV-betagal plasmids as control. Identical studies were also conducted using the radiomimetic drug, bleomycin. RESULTS: Growth hormone protects CHO-4 cells from bleomycin- and radiation-induced cell death. In pHIV-LUC transfected cells, a time-dependent decrease in luciferase activity was observed after irradiation in the absence of growth hormone. However, cells pretreated with this hormone maintained reporter activity. When cells were transfected with irradiated pHIV-LUC plasmid, only the hormone-treated cells recovered the transcriptional activity. CONCLUSIONS: Growth hormone exerts a radioprotective effect in CHO-4 cells stably transfected with the complementary DNA for the rat growth hormone receptor. The radioprotection is triggered directly by the hormone and it is also observed with bleomycin. The increased survival in response to radiation and bleomycin treatment induced by growth hormone correlates with an enhanced ability of the cells to repair damaged DNA.

scholarly journals Long noncoding RNA FAM225A promotes the malignant progression of gastric cancer through the miR-326/PADI2 axis

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Xiang Ma ◽  
Gang Wang ◽  
Hao Fan ◽  
Zengliang Li ◽  
Wangwang Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
In Vitro Assays ◽  
Advanced Tumor Stage ◽  
Advanced Tumor ◽  
Mechanistic Investigation

AbstractGastric cancer (GC) is a global health problem and further studies of its molecular mechanisms are needed to identify effective therapeutic targets. Although some long noncoding RNAs (lncRNAs) have been found to be involved in the progression of GC, the molecular mechanisms of many GC-related lncRNAs remain unclear. In this study, a series of in vivo and in vitro assays were performed to study the relationship between FAM225A and GC, which showed that FAM225A levels were correlated with poor prognosis in GC. Higher FAM225A expression tended to be correlated with a more profound lymphatic metastasis rate, larger tumor size, and more advanced tumor stage. FAM225A also promoted gastric cell proliferation, invasion, and migration. Further mechanistic investigation showed that FAM225A acted as a miR-326 sponge to upregulate its direct target PADI2 in GC. Overall, our findings indicated that FAM225A promoted GC development and progression via a competitive endogenous RNA network of FAM225A/miR-326/PADI2 in GC, providing insight into possible therapeutic targets and prognosis of GC.

scholarly journals The lncRNA H19 Promotes Cell Proliferation by Competitively Binding to miR-200a and Derepressing β-Catenin Expression in Colorectal Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Weiwei Yang ◽  
Ning Ning ◽  
Xiaoming Jin
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Noncoding Rna ◽  
Target Gene ◽  
Colon Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Cell Viability Assay ◽  
Viability Assay

H19, a paternally imprinted noncoding RNA, has been found to be overexpressed in various cancers, including colorectal cancer (CRC), and may function as an oncogene. However, the mechanism by which H19 regulates CRC progression remains poorly understood. In this study, we aimed to assess H19 expression levels in CRC tissues, determine the effect of H19 on CRC proliferation, and explore the mechanism by which H19 regulates the proliferation of CRC. We measured H19 expression using qRT-PCR and analysed the effects of H19 on colon cancer cell proliferation via cell growth curve, cell viability assay, and colony formation assays. To elucidate the mechanism underlying these effects, we analysed the interactions between H19 and miRNAs and identified the target gene to which H19 and miRNA competitively bind using a series of molecular biological techniques. H19 expression was upregulated in CRC tissues compared with adjacent noncancerous tissues. H19 overexpression facilitated colon cancer cell proliferation, whereas H19 knockdown inhibited cell proliferation. miR-200a bound to H19 and inhibited its expression, thereby decreasing CRC cell proliferation. β-Catenin was identified as a target gene of miR-200a. H19 regulated β-catenin expression and activity by competitively binding to miR-200a. H19 promotes cell proliferation by competitively binding to miR-200a and derepressing β-catenin in CRC.

scholarly journals Psoralen alleviates high glucose-induced HK-2 cell injury by a mechanism involving miR-847 upregulation

2020 ◽  
Author(s):  
Yongtao Lin ◽  
Lili Zhong ◽  
Hailun Li ◽  
Yong Xu ◽  
Xiang Li ◽  
...  
Keyword(s):  
Western Blot ◽  
High Glucose ◽  
Molecular Mechanisms ◽  
Cell Injury ◽  
Human Kidney ◽  
Cell Viability Assay ◽  
Viability Assay ◽  
Patients With Diabetes ◽  
Apoptosis Assay ◽  
Underlying Mechanisms

Abstract Background Diabetic nephropathy (DN) causes the vast proportion of excess mortality for patients with diabetes. Novel therapeutic approaches slowing down its incidence is still lacking. Psoralen is the major active ingredient of Psoralea corylifolia Linn. (PCL), which was used to treat a number of diseases. In this study, we aimed to investigate whether psoralen could alleviate DN and to explore the underlying mechanisms. Methods Cell viability assay and immunofluorescence were used to evaluate the effect of psoralen on high glucose (HG)-stimulated human kidney HK-2 cells. RT-qPCR was used to detect the expressions of miRNA in cells. Cell transfection, apoptosis assay and Western blot were further performed to explore the underlying molecular mechanisms. Results Psoralen alleviated HG-induced viability decrease of HK-2 cells via inhibiting apoptosis. Meanwhile, the secretion of inflammatory cytokines and extracellular matrix (ECM) accumulation induced by HG in HK-2 cells were also decreased by psoralen. In addition, the expression of miR-874 in HK-2 cells was significantly upregulated by psoralen. Western blot assays indicated that psoralen inhibiting TGF-β1/Smad2 signaling via upregulation of miR-874. Conclusion This study demonstrated that psoralen could significantly alleviate HG-induced HK-2 cell injury via upregulation of miR-874. Therefore, psoralen might serve as an agent for the treatment of DN.

scholarly journals The association between polymorphism of the long noncoding RNA, Plasmacytoma variant translocation 1, and the risk of gastric cancer

Medicine ◽  
2021 ◽  
Vol 100 (48) ◽  
pp. e27773
Author(s):  
Jae Ho Park ◽  
Eun-Heui Jin ◽  
Jang Hee Hong ◽  
Sang-Il Lee ◽  
Jae Kyu Sung
Keyword(s):  
Gastric Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Variant Translocation

scholarly journals Downregulated Expression of linc-ROR in Gastric Cancer and Its Potential Diagnostic and Prognosis Value

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Xiuchong Yu ◽  
Haixiang Ding ◽  
Yijiu Shi ◽  
Liangwei Yang ◽  
Jiaming Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Noncoding Rna ◽  
Area Under The Curve ◽  
Diagnostic Value ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Polymerase Chain ◽  
Long Intergenic Noncoding Rna ◽  
Clinical Potential ◽  
The Relationship

Background. Gastric cancer (GC) is one of the global mortality diseases and has a poor prognosis due to the lack of ideal tumor biomarkers. Numerous studies have shown that long noncoding RNAs (lncRNAs) can affect the occurrence and development of cancer through a variety of signaling pathways. The abnormal expression and specificity of lncRNAs in tumors make them potential biomarkers of cancers. Nevertheless, the diagnostic roles of lncRNAs in GC have been poorly understood. So this study focuses on the clinical diagnostic value of lncRNAs in GC. Materials and Methods. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to investigate the expression of the linc-ROR (long intergenic noncoding RNA, regulator of reprogramming) in 105 paired GC tissues and adjacent normal tissues. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were established to assess the diagnostic value of linc-ROR. The relationship between expression of linc-ROR and clinicopathological factors of patients with GC was further explored. Kaplan-Meier analysis was performed to evaluate the prognostic value of linc-ROR expression. Results. The linc-ROR expression level was significantly decreased in GC tissues compared with its adjacent nontumor tissues ( n = 105 , P < 0.001 ). We also discovered that linc-ROR was evidently downregulated in 68.6% (72/105) of GC tissues. The AUC’s value of linc-ROR was up to 0.6495, with sensitivity and specificity of 0.7524 and 0.5143, respectively. Intriguingly, the linc-ROR expression levels were obviously associated with tumor differentiation ( P = 0.004 ). Notably, the overall survival rate of GC patients with high expression of linc-ROR was significantly higher than those with low expression. Conclusion. Our data revealed that linc-ROR has clinical potential as a biomarker for the diagnosis of GC and assessment of its prognosis.

scholarly journals LncRNA DANCR promotes migration and invasion through suppression of lncRNA-LET in gastric cancer cells

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Zhengqiang Mao ◽  
Hang Li ◽  
Botao Du ◽  
Kai Cui ◽  
Yuguang Xing ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Clinical Stage ◽  
Epigenetic Mechanism ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Gastrointestinal Malignancies ◽  
Cell Migration And Invasion

Gastric cancer (GC) is one of the most prevalent gastrointestinal malignancies. Long noncoding RNA (lncRNA) DANCR is a newly identified oncogenic lncRNA. However, the functional role and underlying molecular mechanisms of DANCR involved in GC progress remain unclear. In the present study, we investigated the biological function and underlying mechanisms of DANCR in GC cell migration and invasion. The results showed that knockdown of DANCR inhibited migration and invasion of GC cells, whereas overexpression of DANCR showed the opposite effect. Further investigation demonstrated that lncRNA-LET was a bona fide target gene of DANCR. In addition, high DANCR and low lncRNA-LET were significantly correlated with lymph node metastasis and late clinical stage. DANCR associated with EZH2 and HDAC3 to epigenetically silence lncRNA-LET and then regulated GC migration and invasion. Taken together, these findings indicate an important role for DANCR–lncRNA-LET axis in GC cell migration and invasion, and reveal a novel epigenetic mechanism for lncRNA-LET silencing.

scholarly journals Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-Catenin pathway

2020 ◽  
Author(s):  
Jiacheng Cao ◽  
Xing Zhang ◽  
Penghui Xu ◽  
Haixiao Wang ◽  
Sen Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Glutamine Metabolism ◽  
Diagnosis And Treatment ◽  
Luciferase Reporter ◽  
Migration And Invasion

Abstract Background : Gastric cancer (GC) is one of the most common malignant tumors worldwide. Currently, the overall survival rate of GC is still unsatisfactory despite progress in diagnosis and treatment. Therefore, studying the molecular mechanisms involved in GC is vital for diagnosis and treatment. CircRNAs, a type of noncoding RNA, have been proven to act as miRNA sponges that can widely regulate various cancers. By this mechanism, circRNA can regulate tumors at the genetic level by releasing miRNA from inhibiting its target genes. The WNT2/β-Catenin regulatory pathway is one of the canonical signaling pathways in tumors. It can not only promote the development of tumors but also provide energy for tumor growth through cell metabolism (such as glutamine metabolism). Methods: Through RNA sequencing, we found that hsa_circ_0008259 (circLMO7) was highly expressed in GC tissues. After verifying the circular characteristics of circLMO7, we determined the downstream miRNA (miR-30a-3p) of circLMO7 by RNA pull-down and luciferase reporter assays. We verified the effect of circLMO7 and miR-30a-3p on GC cells through a series of functional experiments, including colony formation, 5-ethynyl-2’-deoxyuridine and Transwell assays. Through Western blot and immunofluorescence analyses, we found that WNT2 was the downstream target gene of miR-30a-3p and further confirmed that the circLMO7-miR-30a-3p-WNT2 axis could promote the development of GC. In addition, measurement of related metabolites confirmed that this axis could also provide energy for the growth of GC cells through glutamine metabolism. We found that circLMO7 could promote the growth and metastasis of GC in vivo by the establishment of nude mouse models. Finally, we also demonstrated that HNRNPL could bind to the flanking introns of the circLMO7 exons to promote circLMO7 cyclization. Results: CircLMO7 acted as a miR-30a-3p sponge affecting the WNT2/β-Catenin pathway to promote the proliferation, migration and invasion of GC cells. Moreover, animal results also showed that circLMO7 could promote GC growth and metastasis in vivo . CircLMO7 could also affect the glutamine metabolism of GC cells through the WNT2/β-Catenin pathway to promote its malignant biological function. In addition, we proved that HNRNPL could promote the self-cyclization of circLMO7. Conclusions: CircLMO7 promotes the development of GC by releasing the inhibitory effect of miR-30a-3p on its target gene WNT2.

scholarly journals Long Noncoding RNA UCA1 in Gastrointestinal Cancers: Molecular Regulatory Roles and Patterns, Mechanisms, and Interactions

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Suaidah Ramli ◽  
Maw Shin Sim ◽  
Rhanye M. Guad ◽  
Subash C. B Gopinath ◽  
Vetriselvan Subramaniyan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Reading Frame ◽  
Hepatobiliary Cancer ◽  
Gi Cancer ◽  
Gi Cancers ◽  
Cancer Phenotypes ◽  
Underlying Mechanisms

The rising trend of gastrointestinal (GI) cancer has become a global burden due to its aggressive nature and poor prognosis. Long noncoding RNAs (lncRNAs) have recently been reported to be overexpressed in different GI cancers and may contribute to cancer progression and chemoresistance. They are featured with more than 200 nucleotides, commonly polyadenylated, and lacking an open reading frame. LncRNAs, particularly urothelial carcinoma-associated 1 (UCA1), are oncogenes involved in regulating cancer progression, such as cell proliferation, invasion, migration, and chemoresistance, particularly in GI cancer. This review was aimed to present an updated focus on the molecular regulatory roles and patterns of lncRNA UCA1 in progression and chemoresistance of different GI cancers, as well as deciphering the underlying mechanisms and its interactions with key molecules involved, together with a brief presentation on its diagnostic and prognostic values. The regulatory roles of lncRNA UCA1 are implicated in esophageal cancer, gastric cancer, pancreatic cancer, hepatobiliary cancer, and colorectal cancer, where they shared similar molecular mechanisms in regulating cancer phenotypes and chemoresistance. Comparatively, gastric cancer is the most intensively studied type in GI cancer. LncRNA UCA1 is implicated in biological roles of different GI cancers via interactions with various molecules, particularly microRNAs, and signaling pathways. In conclusion, lncRNA UCA1 is a potential molecular target for GI cancer, which may lead to the development of a novel chemotherapeutic agent. Hence, it also acts as a potential diagnostic and prognostic marker for GI cancer patients.

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