Antiproliferative effect of urolithin A, the ellagic acid-derived colonic metabolite, on hepatocellular carcinoma HepG2. 2. 15 cells by targeting Lin28a/let-7a axis
Braz. j. med. biol. res
; 51(7): e7220, 2018. tab, graf
Article
in En
| LILACS
| ID: biblio-889115
Responsible library:
BR1.1
ABSTRACT
An abnormality in the Lin28/let-7a axis is relevant to the progression of hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC), which could be a novel therapeutic target for this malignant tumor. The present study aimed to investigate the antiproliferative and anti-invasive effects of urolithin A in a stable full-length HBV gene integrated cell line HepG2.2.15 using CCK-8 and transwell assays. The RNA and protein expressions of targets were assessed by quantitative PCR and western blot, respectively. Results revealed that urolithin A induced cytotoxicity in HepG2.2.15 cells, which was accompanied by the cleavage of caspase-3 protein and down-regulation of Bcl-2/Bax ratio. Moreover, urolithin A suppressed the protein expressions of Sp-1, Lin28a, and Zcchc11, and elevated the expression of microRNA let-7a. Importantly, urolithin A also regulated the Lin28a/let-7a axis in transient HBx-transfected HCC HepG2 cells. Furthermore, urolithin A decelerated the HepG2.2.15 cell invasion, which was involved in suppressing the let-7a downstream factors HMGA2 and K-ras. These findings indicated that urolithin A exerted the antiproliferative effect by regulating the Lin28a/let-7a axis and may be a potential supplement for HBV-infected HCC therapy.
Key words
Full text:
1
Index:
LILACS
Main subject:
RNA-Binding Proteins
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Carcinoma, Hepatocellular
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Coumarins
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MicroRNAs
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Liver Neoplasms
Limits:
Humans
Language:
En
Journal:
Braz. j. med. biol. res
Journal subject:
BIOLOGIA
/
MEDICINA
Year:
2018
Type:
Article
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Project document