miR-122-5p Restrains Pancreatic Cancer Cell Growth and Causes Apoptosis by Negatively Regulating ASCT2.
Anticancer Res
; 43(10): 4379-4388, 2023 Oct.
Article
in En
| MEDLINE
| ID: mdl-37772564
ABSTRACT
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 ANDMETHODS:
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreatic Neoplasms
/
MicroRNAs
Type of study:
Etiology_studies
Limits:
Humans
Language:
En
Journal:
Anticancer Res
Year:
2023
Document type:
Article