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Title:
The lncRNA MACC1-AS1 promotes gastric cancer cell metabolic plasticity via AMPK/Lin28 mediated mRNA stability of MACC1 | Molecular Cancer
Description:
Background Metabolic plasticity has been increasingly thought to be a determinant of tumor growth and metastasis. MACC1, a transcriptional regulator of MET, was recognized as an oncogene in gastric cancer (GC); however, its transcriptional or post-translational regulation was not clear. We previously reported the metabolic role of MACC1 in glycolysis to promote GC progression. MACC1-AS1 is the antisense lncRNA of MACC1, yet its function was previously unknown. Methods We profiled and analyzed the expression of MACC1-AS1 utilizing the TCGA database as well as in situ hybridization using 123 pairs of GC tissues and matched adjacent normal gastric mucosa tissues (ANTs). The biological role of MACC1-AS1 in cell growth and metastasis was determined by performing in vitro and in vivo functional experiments. Glycolysis and antioxidant capabilities were assayed to examine its metabolic function. Further, the specific regulatory effect of MACC1-AS1 on MACC1 was explored transcriptionally and post-transcriptionally. Results MACC1-AS1 was shown to be expressed significantly higher in GC tissues than in ANTs, which predicted poor prognosis in GC patients. MACC1-AS1 promoted GC cell proliferation and inhibited cell apoptosis under metabolic stress. Mechanistically, MACC1-AS1 stabilized MACC1 mRNA and post-transcriptionally augmented MACC1 expression. Further, MACC1-AS1 was shown to mediate metabolic plasticity through MACC1 upregulation and subsequent enhanced glycolysis and anti-oxidative capabilities, and this was suggested to be coordinated by the AMPK/Lin28 pathway. Conclusions Elevated expression of MACC1-AS1 in gastric cancer tissues is linked to poor prognosis and promotes malignant phenotype upon cancer cells. MACC1-AS1 is elevated under metabolic stress and facilitates metabolic plasticity by promoting MACC1 expression through mRNA stabilization. Our study implicates lncRNA MACC1-AS1 as a valuable biomarker for GC diagnosis and prognosis.
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Keywords {🔍}
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Topics {✒️}
plenti-ef1a-luc-f2a-puro-cmv-macc1-as1 constructs plkd-u6-shrna-ef1a-luc-f2a-puro-macc1 ros scavenger n-acetyl-l-cysteine macc1-as1/macc1 axis functioned large-scale clip-seq data pet-ct image analysis article download pdf macc1-as1 overexpression group n-acetyl-l-cysteine lin28-mediated post-transcriptional regulation macc1-as1 promotes migration macc1-as1 expression mitigated profile gene expression cyclohexamide-induced macc1 degradation macc1-as1 promoted migration sds–polyacrylamide gel electrophoresis serial saline-sodium citrate hgf/c-met axis macc1-as1 regulates glycolysis macc1-as1 partially abrogated macc1-as1 positive group macc1-as1 promoted atp macc1-as1 promoted glutathione macc1-as1 negative group pgl3-macc1-3′utr vector kaplan–meier analysis showed macc1-as1 enhances glycolysis macc1-as1 promoted hk synthetic sequence-scrambled sirna macc1-as1 overexpression groups biotin-labeled macc1-as1 target hgf/c-met showed macc1-as1 enhanced hgf/c-met inhibitors measure macc1-as1 expression antisense macc1-as1 sequence forming rna-rna complexes firefly/renilla luciferase assays nadp+/nadph quantification kit protein–rna interaction networks macc1-as1 partially reversed high macc1-as1 expression macc1 shrna-induced glut1 reduced disease-free survival ampk inhibition-induced suppression fluorescent-tagged secondary antibody promotes metabolic plasticity glucose deprivation-induced expression gssg/gsh ratios decreased gsh/gssg quantification kit
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headline:The lncRNA MACC1-AS1 promotes gastric cancer cell metabolic plasticity via AMPK/Lin28 mediated mRNA stability of MACC1
description:Metabolic plasticity has been increasingly thought to be a determinant of tumor growth and metastasis. MACC1, a transcriptional regulator of MET, was recognized as an oncogene in gastric cancer (GC); however, its transcriptional or post-translational regulation was not clear. We previously reported the metabolic role of MACC1 in glycolysis to promote GC progression. MACC1-AS1 is the antisense lncRNA of MACC1, yet its function was previously unknown. We profiled and analyzed the expression of MACC1-AS1 utilizing the TCGA database as well as in situ hybridization using 123 pairs of GC tissues and matched adjacent normal gastric mucosa tissues (ANTs). The biological role of MACC1-AS1 in cell growth and metastasis was determined by performing in vitro and in vivo functional experiments. Glycolysis and antioxidant capabilities were assayed to examine its metabolic function. Further, the specific regulatory effect of MACC1-AS1 on MACC1 was explored transcriptionally and post-transcriptionally. MACC1-AS1 was shown to be expressed significantly higher in GC tissues than in ANTs, which predicted poor prognosis in GC patients. MACC1-AS1 promoted GC cell proliferation and inhibited cell apoptosis under metabolic stress. Mechanistically, MACC1-AS1 stabilized MACC1 mRNA and post-transcriptionally augmented MACC1 expression. Further, MACC1-AS1 was shown to mediate metabolic plasticity through MACC1 upregulation and subsequent enhanced glycolysis and anti-oxidative capabilities, and this was suggested to be coordinated by the AMPK/Lin28 pathway. Elevated expression of MACC1-AS1 in gastric cancer tissues is linked to poor prognosis and promotes malignant phenotype upon cancer cells. MACC1-AS1 is elevated under metabolic stress and facilitates metabolic plasticity by promoting MACC1 expression through mRNA stabilization. Our study implicates lncRNA MACC1-AS1 as a valuable biomarker for GC diagnosis and prognosis.
datePublished:2018-03-06T00:00:00Z
dateModified:2018-03-06T00:00:00Z
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MACC1-AS1
MACC1
Long non-coding RNA
Gastric cancer
Metabolic plasticity
mRNA stability
Cancer Research
Oncology
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headline:The lncRNA MACC1-AS1 promotes gastric cancer cell metabolic plasticity via AMPK/Lin28 mediated mRNA stability of MACC1
description:Metabolic plasticity has been increasingly thought to be a determinant of tumor growth and metastasis. MACC1, a transcriptional regulator of MET, was recognized as an oncogene in gastric cancer (GC); however, its transcriptional or post-translational regulation was not clear. We previously reported the metabolic role of MACC1 in glycolysis to promote GC progression. MACC1-AS1 is the antisense lncRNA of MACC1, yet its function was previously unknown. We profiled and analyzed the expression of MACC1-AS1 utilizing the TCGA database as well as in situ hybridization using 123 pairs of GC tissues and matched adjacent normal gastric mucosa tissues (ANTs). The biological role of MACC1-AS1 in cell growth and metastasis was determined by performing in vitro and in vivo functional experiments. Glycolysis and antioxidant capabilities were assayed to examine its metabolic function. Further, the specific regulatory effect of MACC1-AS1 on MACC1 was explored transcriptionally and post-transcriptionally. MACC1-AS1 was shown to be expressed significantly higher in GC tissues than in ANTs, which predicted poor prognosis in GC patients. MACC1-AS1 promoted GC cell proliferation and inhibited cell apoptosis under metabolic stress. Mechanistically, MACC1-AS1 stabilized MACC1 mRNA and post-transcriptionally augmented MACC1 expression. Further, MACC1-AS1 was shown to mediate metabolic plasticity through MACC1 upregulation and subsequent enhanced glycolysis and anti-oxidative capabilities, and this was suggested to be coordinated by the AMPK/Lin28 pathway. Elevated expression of MACC1-AS1 in gastric cancer tissues is linked to poor prognosis and promotes malignant phenotype upon cancer cells. MACC1-AS1 is elevated under metabolic stress and facilitates metabolic plasticity by promoting MACC1 expression through mRNA stabilization. Our study implicates lncRNA MACC1-AS1 as a valuable biomarker for GC diagnosis and prognosis.
datePublished:2018-03-06T00:00:00Z
dateModified:2018-03-06T00:00:00Z
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MACC1-AS1
MACC1
Long non-coding RNA
Gastric cancer
Metabolic plasticity
mRNA stability
Cancer Research
Oncology
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