Baicalein, a Natural Anti-Cancer Compound, Alters MicroRNA Expression Profiles in Bel-7402 Human Hepatocellular Carcinoma Cells.

Abstract

BACKGROUND/AIMS:

Baicalein has been shown to possess significant anti-hepatoma activity by inhibiting cell proliferation. Whether the anti-proliferative effect of baicalein is related to its modulation of miRNA expression in hepatocellular carcinoma (HCC) is still unknown.

METHODS:

The anti-proliferative effects of baicalein on HCC cell line Bel-7402 was assessed by detecting the proliferation activity, cell cycle distribution, expression changes of p21/CDKN1A, P27/CDKN1B, total Akt and phosphoryted AKT. Microarray analysis was conducted to determine the miRNA expression profiles in baicalein-treated or untreated Bel-7402 cells and then validated by qRT-PCR in two HCC cell lines (Bel-7402 and Hep3B). The gain-of-function of miR-3127-5p was performed by detecting anti-proliferative effects after transfecting miRNA mimics in cells. Finally, the expression level of miR-3127-5p in different HCC cell lines was determined by qRT-PCR.

RESULTS:

Baicalein was able to inhibit the proliferation of Bel-7402 cells by inducing cell cycle arrest at the S and G2/M phase via up-regulating the expression of p21/CDKN1A and P27/CDKN1B and suppressing the PI3K/Akt pathway. Baicalein could alter the miRNA expression profiles in Bel-7402 cells. Putative target genes for differentially expressed miRNAs could be enriched in terms of cell proliferation regulation, cell cycle arrest and were mainly involved in MAPK, PI3K-Akt, Wnt, Hippo and mTOR signaling pathways. MiR- 3127-5p, one of up-regulated miRNAs, exhibits low expression level in several HCC cell lines and its overexpression could inhibit cell growth of Bel-7402 and Hep3B cell lines by inducing S phase arrest by up-regulating the expression of p21and P27 and repressing the PI3K/Akt pathway.

CONCLUSIONS:

Modulation of miRNA expression may be an important mechanism underlying the anti-hepatoma effects of baicalein.

• Authors: Beibei Bie, Jin Sun, Jun Li, Ying Guo, Wei Jiang, Chen Huang, Jun Yang, Zongfang Li
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 41 Issue 4 Pg. 1519-1531 ( 2017) ISSN: 1421-9778 [Electronic] Germany
• PMID: 28351032 (Publication Type: Journal Article)
• Copyright: © 2017 The Author(s)Published by S. Karger AG, Basel.

Chemical References

• Antineoplastic Agents, Phytogenic
• Flavanones
• MIRN3127 microRNA, human
• MicroRNAs
• Neoplasm Proteins
• RNA, Neoplasm
• baicalein

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Carcinoma, Hepatocellular (drug therapy, metabolism)
• Cell Cycle (drug effects)
• Flavanones
• Gene Expression Regulation, Neoplastic (drug effects)
• Hep G2 Cells
• Humans
• Liver Neoplasms (drug therapy, metabolism)
• MAP Kinase Signaling System (drug effects)
• MicroRNAs (biosynthesis)
• Neoplasm Proteins (biosynthesis)
• RNA, Neoplasm (biosynthesis)