Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.22.56 (caspase-3)
 35,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Long non-coding RNAs (IncRNAs) play important roles in various biological processes, such as transcriptional regulation, cell growth and tumorigenesis. However, little is known about the role of IncRNA HIF 1 alpha-antisense RNA 1 (HIF1a-AS1) in regulating the proliferation and apoptosis of vascular smooth muscle cells (VSMCs) and the expression of HIF1a-AS1 in serum of thoracoabdominal aortic aneurysm (TAAA) patients. The cell viability was detected by the CCK8 assay. The cell apoptosis was assessed by annexin V-PI double-labeling staining. Expression of genes and proteins were analyzed by real-time PCR and western blotting, respectively. Cells were transfected with siRNAs as a gene silencing method. In serum of TAAA patients, the expression of HIF1a-AS1 was significantly increased (superior to 6-fold) compared to the normal control. Moreover, Palmitic acid (PA) induced cell apoptosis in VSMCs in a time- and dose-dependent manner, and the proportion of the apoptotic cells had gained as compared to untreatment group. PA also induced up-regulation expression of HIF1a-AS1. We also found that transfection of cells with HIF1a-AS1 siRNA decreased the expression of caspase-3 and caspase-8 and increased the expression of Bcl2, and protected PA-induced cell apoptosis in VSMCs. HIF1a-AS1 was overexpressed in the TAAA and the interaction between HIF1a-AS1 and apoptotic proteins plays a key role in the proliferation and apoptosis of VSMCs in vitro, which may contribute to the pathogenesis of TAAA.
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PMID:Long noncoding RNA HIF1A-AS1A reduces apoptosis of vascular smooth muscle cells: implications for the pathogenesis of thoracoabdominal aorta aneurysm. 2606 99

Recent studies have shown that long non-coding RNAs (lncRNAs) are involved in a variety of biological processes and diseases in humans, including cancer. Our study serves as the first comprehensive analysis of lncRNA TP73-AS1 in esophageal cancer. We utilized a lncRNA microarray to analyze the expression profile of lncRNAs in esophageal squamous cell carcinoma. Our results show that lncRNA TP73-AS1 and BDH2 levels are generally upregulated in esophageal cancer tissues and are strongly correlated with tumor location or TNM stage in clinical samples. LncRNA TP73-AS1 knockdown inhibited BDH2 expression in EC9706 and KYSE30 cells, whereas BDH2 knockdown repressed esophageal cancer cell proliferation and induced apoptosis via the caspase-3 dependent apoptotic pathway. Overexpression of BDH2 in lncRNA TP73-AS1 knockdown cells partially rescued cell proliferation rates and suppressed apoptosis. In mouse xenografts, tumor size was reduced in lncRNA TP73-ASI siRNA-transfected tumors, suggesting that downregulation of lncRNA TP73-AS1 attenuated EC proliferation in vitro and in vivo. In addition, BDH2 or lncRNA TP73-AS1 knockdown enhanced the chemosensitivity of esophageal cancer cells to 5-FU and cisplatin. Our results suggest that lncRNA TP73-AS1 may be a novel prognostic biomarker that could serve as a potential therapeutic target for the treatment of esophageal cancer.
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PMID:Knockdown of long non-coding RNA TP73-AS1 inhibits cell proliferation and induces apoptosis in esophageal squamous cell carcinoma. 2679 87

Long noncoding RNAs (lncRNAs) play roles in the tumorigenesis, proliferation and metastasis of tumor cells. Previous studies indicate that the transcription factor Sp1 is responsible for transcription of the XIAP gene, but it is unknown whether lncRNAs are involved in XIAP transcription. Herein, we identified a novel lncRNA, denoted as XIAP-AS1, transcribed from the first intron of the complementary strand of the XIAP gene. Using RNA FISH, cell fractionation and qRT-PCR, XIAP-AS1 was determined to be located primarily in the nucleus. After various XIAP-AS1 deletion mutants were expressed, RIP assays showed that only the full-length XIAP-AS1 RNA interacted with Sp1 and thereby participated in XIAP transcription. ChIP assays showed that XIAP-AS1 knockdown decreased the binding of Sp1 to the promoter region of XIAP. XIAP-AS1 knockdown promoted tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in gastric tumor cells, as cleaved caspase-3 and caspase-9 was detected. Moreover, in an in vivo mouse xenograft model, tumor cell proliferation was inhibited by XIAP-AS1 knockdown in response to TRAIL administration. In conclusion, our results indicate that XIAP-AS1 is involved in XIAP transcription by interacting with Sp1. Additionally, XIAP-AS1 is a potential target for TRAIL-induced apoptosis in gastric cancer cells.
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PMID:The long noncoding RNA XIAP-AS1 promotes XIAP transcription by XIAP-AS1 interacting with Sp1 in gastric cancer cells. 2879 27

Lung cancer is among the leading causes of cancer-associated mortality worldwide, with a low 5-year survival rate of 16.1%. However, the underlying molecular mechanisms behind lung cancer tumorigenesis remain largely unknown. Long non-coding RNAs (lncRNAs) have been demonstrated to serve a function in the tumorigenesis of multiple types of cancer. The objective of the present study was to identify the function of a newly identified lncRNA zinc finger E-box-binding homeobox 2 antisense RNA 1 (ZEB2-AS1) in human lung cancer. Results demonstrated that the transcript level of ZEB2-AS1 in human lung cancer was markedly upregulated in vivo and in vitro. The knockdown of ZEB2-AS1 in A549 and NCI-H292 cells, and the overexpression of ZEB2-AS1 in H-125 and H1975 cells, altered colony formation and cell proliferative rate, as examined using colony formation and cell proliferation assays. Western blot analysis revealed that the knockdown of ZEB2-AS1 in A549 and NCI-H292 cells increased the protein levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3 and -9, upregulated the relative activities of caspase-3 and -9, and had no observable effect on caspase-8 activity. Similarly, the overexpression of ZEB2-AS1 in H-125 and H1975 cells resulted in decreased expression of caspase-3, caspase-9, Bcl-2 and Bax. The results identified the effects of lncRNA ZEB2-AS1 on lung cancer progression through promoting its proliferation and inhibiting cell apoptosis, indicating that ZEB2-AS1 may serve as a novel prognostic factor for the diagnosis and treatment of human lung cancer in the clinic.
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PMID:Long non-coding RNA ZEB2-AS1 promotes proliferation and inhibits apoptosis in human lung cancer cells. 2955 61

Ovarian cancer is a markedly heterogeneous malignancy characterized by various histological subtypes. Molecular biomarkers have been indicated to serve significant functions in the early diagnosis and treatment of early-stage ovarian cancer. However, the detailed mechanism underlying the tumorigenesis of ovarian cancer remains unclear. The present study aimed to identify a novel long non-coding RNA in patients with ovarian cancer. Nicotinamide nucleotide transhydrogenase-antisense 1 (NNT-AS1) was markedly downregulated in patients with ovarian cancer and in cultured human ovarian cancer cells. Knockdown of NNT-AS1 in the human ovarian cancer cell lines HO-8910 and SK-OV-3 promoted colony formation and arrested the cell cycle at G0/G1 phase. Furthermore, Transwell demonstrated that the downregulation of NNT-AS1 increased cell migration and invasion by ~60 and 70%, respectively, in HO-8910 and SK-OV-3 cells. Furthermore, cell apoptosis was inhibited by the transfection of siNNT-AS1 in the two cell lines, whereas the relative activities of caspase-3 and caspase-9 were decreased. These results indicated a protective function of NNT-AS1 in human ovarian cancer, providing novel insights into the diagnosis and treatment of ovarian cancer in clinical settings.
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PMID:Long non-coding RNA NNT-AS1 contributes to cell proliferation, metastasis and apoptosis in human ovarian cancer. 2980 55

Cholangiocarcinoma (CCA) is one of the most aggressive malignancies with increasing incidence worldwide. Various evidence documents that abnormally expressed long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and progression. TP73-AS1 is a novel cancer-related lncRNA that contributes to the development of several malignancies. However, its clinical value and potential effects on CCA remains unknown. RT-qPCR was used to measure the expression levels of TP73-AS1 in CCA tissues and paired non-tumor tissues and the association between TP73-AS1 expression and clinicopathological characteristics was analyzed. In addition, the functional roles of TP73-AS1 in CCA were detected both in vitro and in vivo. The results illustrated that TP73-AS1 transcription is enhanced in both CCA tissue samples and cell lines, and this upregulation is closely associated with larger tumor size (p=0.008) and advanced TNM stage (p=0.026) in patients with CCA. For the part of functional assays, silencing of TP73-AS1 could attenuate CCA cell growth both in vitro and in vivo. Additionally, silencing of TP73-AS1 facilitates apoptosis via activating caspase-3 and caspase-9. Importantly, TP73-AS1 expression did not affect HIBEC cell growth and apoptosis. Moreover, TP73-AS1 could also facilitate migration and invasion potential of CCA cells. Collectively, these findings may help to develop a potential therapeutic target for the patients with CCA.
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PMID:Enhanced expression of lncRNA TP73-AS1 predicts adverse phenotypes for cholangiocarcinoma and exerts oncogenic properties in vitro and in vivo. 2996 69

Gastric cancer (GC) is a deadly disease with high incidence worldwide in recent years. Long noncoding RNAs (lncRNAs) were found to play imperative roles in many biological processes, such as cancer development and progression. Specifically, TP73-AS1, a novel cancer-related lncRNA, was documented to be up-regulated in several malignancies, but the clinical significance and functional role of TP73-AS1 in GC is still unknown. RT-qPCR was performed to evaluate TP73-AS1 transcription in GC tissue specimens and cell lines. In addition, the correlation between TP73-AS1 transcription and clinicopathologic features was further evaluated. Moreover, the effects of TP73-AS1 on GC cell were measured in vitro and in vivo. The data documented that TP73-AS1 was enhanced in GC tissues and cells, and TP73-AS1 transcription level was tightly associated with tumor size, TNM stage, and overall survival in 76 GC patients. What's more, decreased TP73-AS1 could restrain cell growth and colony-forming capacity and promoted apoptosis partly by regulating Bcl-2/caspase-3 pathway. Importantly, TP73-AS1 could promote xenograft growth in vivo. Silencing of TP73-AS1 inhibited GC cell migratory and invasive properties partly by reversing snail-mediated epithelial-to-mesenchymal transition (EMT). Collectively, this study may help to develop the treatment strategy for GC.
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PMID:Enhanced expression of lncRNA TP73-AS1 predicts unfavorable prognosis for gastric cancer and promotes cell migration and invasion by induction of EMT. 3011 90

Total knee arthroplasty (TKA) is the most common and cost-effective treatment for older adults with long-standing osteoarthritis. During TKA, muscle cells suffer from prolonged oxygen deficiency, which leads to altered cell metabolism that reduces the energy demand and maintains cell homeostasis before blood flow is restored. This study focused on the role of the lncRNA muscleblind-like 1 antisense RNA 1 (MBNL1-AS1) in protecting sevoflurane-pretreated mice against ischemia-reperfusion (I/R) injury after TKA, as well as the elucidation of the potential associated mechanism. Identification of differentially expressed lncRNAs was performed using the microarray dataset GSE21164, which was extracted from the GEO database. Target genes of the lncRNA were determined using Multi-Experiment Matrix (MEM), a dual-luciferase reporter gene assay, and KEGG enrichment analyses. The results showed that MBNL1-AS1 was overexpressed in skeletal muscle cells in mice, while KCNMA1, which was enriched in the cGMP-PKG signaling pathway, was negatively regulated by MBNL1-AS1. Furthermore, I/R mice displayed serious inflammatory reactions. Down-regulation of MBNL1-AS1 increased the expression of KCNMA1, PKGII, VASP, VEGF, Bcl-2, Cyclin D1, Cyclin D3, and Cdc 42 but decreased the expression of Bax, cleaved caspase-3, and cleaved PARP. Furthermore, upon MBNL1-AS1 upregulation, the rate of cell apoptosis increased while the rate of cell proliferation decreased. Our data suggested that down-regulated lncRNA MBNL1-AS1 might promote the proliferation and inhibit the apoptosis of skeletal muscle cells by upregulating KCNMA1 expression via activation of the cGMP-PKG signaling pathway, thus protecting sevoflurane-pretreated mice against I/R injury after TKA.
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PMID:Downregulation of the long noncoding RNA MBNL1-AS1 protects sevoflurane-pretreated mice against ischemia-reperfusion injury by targeting KCNMA1. 3018 81

Lung adenocarcinoma (LUAD) is typically featured by a low 5-year survival rate, hence there is a necessary to investigate new biomarkers in LUAD progression. Competing endogenous RNA (ceRNA) network has been widely reported in the regulation of tumor processes, which is also the main direction of this paper. Based on the data of GEPIA database, lncRNA MAFG-AS1 was upregulated in LUAD tissues, which was associated with poor prognosis of patients. Proliferation or apoptosis of LUAD cells were measured by CCK-8, EdU and caspase-3 activity assays followed by Western blot. The results indicated that silencing of MAFG-AS1 suppressed cell proliferation but induced cell apoptosis. RNA FISH staining showing the cytoplasmic localization of MAFG-AS1 in LUAD cells. Mechanism detection revealed that MAFG-AS1 served as a molecular sponge of miR-744-5p to upregulate its nearby gene MAF bZIP transcription factor G (MAFG) in LUAD cells. Functionally, MAFG overexpression attenuated the cellular processes mediated by MAFG-AS1 knockdown. In summary, this study unveiled the MAFG-AS1/miR-744-5p/MAFG axis in LUAD, providing a potent and promising therapeutic target for LUAD patients.
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PMID:LncRNA MAFG-AS1 boosts the proliferation of lung adenocarcinoma cells via regulating miR-744-5p/MAFG axis. 3121 84

The biologic function as well as the mechanism of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) still remain largely unknown. Long noncoding RNA FGD5 antisense RNA 1 (FGD5-AS1) has been reported to have a promotive effect on other human cancers, but its function in CRC still remains unknown. The expression levels of long noncoding RNA FGD5-AS1, CDCA7 mRNA, and miR-302e were assessed by RT-qPCR. The protein levels of CDCA7 were assessed by Western blot. The function of FGD5-AS1 was detected using cell viability assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, transwell, and caspase-3 activity assay. Additionally, the microRNAs (miRNAs) sponge potential of FGD5-AS1 was examined by RNA immunoprecipitation assay, RNA pull-down assay, and luciferase reporter assay. FGD5-AS1 was increased in colorectal cancer cell lines compared to normal cell lines. Inhibition of FGD5-AS1 suppressed cell proliferation, migration, invasion, and accelerated cell apoptosis in CRC. FGD5-AS1 competitively bound with miR-302e to modulate CDCA7. The inhibiting effects of FGD5-AS1 knockdown on CRC cell proliferation, migration, and invasion, and the promoting effects on CRC cell apoptosis could be revived by miR-302e suppression or CDCA7 upregulation. LncRNA FGD5-AS1 could promote CRC progression through sponging miR-302e and upregulating CDCA7. FGD5-AS1 might serve as a potential therapeutic target for CRC.
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PMID:Long noncoding RNA FGD5-AS1 promotes colorectal cancer cell proliferation, migration, and invasion through upregulating CDCA7 via sponging miR-302e. 3133 96


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