miR-122-5p Restrains Pancreatic Cancer Cell Growth and Causes Apoptosis by Negatively Regulating ASCT2
Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved..
BACKGROUND/AIM: System ASC amino acid transporter-2 (ASCT2) is abnormally highly expressed in tumor cells and closely associated with a poor prognosis, but the regulatory mechanism of abnormally high ASCT2 expression is scarcely investigated. MicroRNAs (miRNAs) that are abnormally expressed regulate gene expression to have either oncogenic or tumor-suppressive effects in pancreatic cancer (PC). MicroRNA-122-5p (miR-122-5p) dysregulation has been seen in various cancer entities, but the biological function of miR-122-5p in PC and its regulation mechanisms remain unknown.
MATERIALS AND METHODS: Western blot and quantitative RT-PCR were used to measure the expression of miR-122-5p, ASCT2, and apoptosis-related proteins. CCK-8 assays were used to elucidate the effect on cell proliferation. Flow cytometry (FCM) assays were utilized to evaluate cell apoptosis. A dual-luciferase reporter assay was utilized to determine if miR-122a-5p directly targeted ASCT2. Glutamine consumption and the α-ketoglutarate (α-KG) and adenosine triphosphate (ATP) contents were determined using respective assays.
RESULTS: MiR-122-5p expression was low whereas ASCT2 expression was high in PC tissues and cells. Overexpressing miR-122-5p restrained pancreatic cancer cell proliferation, accelerated apoptosis, and decreased glutamine consumption, α-ketoglutarate (α-KG) production and ATP generation, whereas suppressing miR-122-5p had the opposite effect. Moreover, the reporter gene test established ASCT2 as a miR-122-5p target. Overexpression of miR-122-5p decreased ASCT2 expression, whereas miR-122-5p repression increased ASCT2 expression. In addition, miR-122-5p also regulated apoptosis-related pathways.
CONCLUSION: MiR-122-5p may function as a tumor suppressor by inhibiting the proliferation, glutamine metabolism, and inducing apoptosis via altering the expression of ASCT2 in pancreatic cancer cells.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
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| Enthalten in: |
Anticancer research - 43(2023), 10 vom: 30. Okt., Seite 4379-4388 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ren, Ping [VerfasserIn] |
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| Links: |
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| Themen: |
0RH81L854J |
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| Anmerkungen: |
Date Completed 02.10.2023 Date Revised 13.12.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.21873/anticanres.16634 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM362687587 |
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| 245 | 1 | 0 | |a miR-122-5p Restrains Pancreatic Cancer Cell Growth and Causes Apoptosis by Negatively Regulating ASCT2 |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. | ||
| 520 | |a BACKGROUND/AIM: System ASC amino acid transporter-2 (ASCT2) is abnormally highly expressed in tumor cells and closely associated with a poor prognosis, but the regulatory mechanism of abnormally high ASCT2 expression is scarcely investigated. MicroRNAs (miRNAs) that are abnormally expressed regulate gene expression to have either oncogenic or tumor-suppressive effects in pancreatic cancer (PC). MicroRNA-122-5p (miR-122-5p) dysregulation has been seen in various cancer entities, but the biological function of miR-122-5p in PC and its regulation mechanisms remain unknown | ||
| 520 | |a MATERIALS AND METHODS: Western blot and quantitative RT-PCR were used to measure the expression of miR-122-5p, ASCT2, and apoptosis-related proteins. CCK-8 assays were used to elucidate the effect on cell proliferation. Flow cytometry (FCM) assays were utilized to evaluate cell apoptosis. A dual-luciferase reporter assay was utilized to determine if miR-122a-5p directly targeted ASCT2. Glutamine consumption and the α-ketoglutarate (α-KG) and adenosine triphosphate (ATP) contents were determined using respective assays | ||
| 520 | |a RESULTS: MiR-122-5p expression was low whereas ASCT2 expression was high in PC tissues and cells. Overexpressing miR-122-5p restrained pancreatic cancer cell proliferation, accelerated apoptosis, and decreased glutamine consumption, α-ketoglutarate (α-KG) production and ATP generation, whereas suppressing miR-122-5p had the opposite effect. Moreover, the reporter gene test established ASCT2 as a miR-122-5p target. Overexpression of miR-122-5p decreased ASCT2 expression, whereas miR-122-5p repression increased ASCT2 expression. In addition, miR-122-5p also regulated apoptosis-related pathways | ||
| 520 | |a CONCLUSION: MiR-122-5p may function as a tumor suppressor by inhibiting the proliferation, glutamine metabolism, and inducing apoptosis via altering the expression of ASCT2 in pancreatic cancer cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ASCT2 | |
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| 700 | 1 | |a Li, Q I |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Qingzhou |e verfasserin |4 aut | |
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