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.

Retracted: Baicalein retards proliferation and collagen deposition by activating p38MAPK‐JNK via microRNA‐29

“…The modulatory effects of BAI on miRs have been reported in multiple diseases, such as pulmonary fibrosis, 15 hepatocellular carcinoma, 14 and bladder F I G U R E 5 miR-29 inhibitor reversed the repressive effects of BAI on the expression of collagen induced by TGF-β1. A, The accumulation of total soluble collagen decreased by BAI was promoted by miR-29 inhibitor in NIH-3T3 cells stimulated with TGF-β1.…”

Baicalein Inhibits Proliferation Activity of Human Colorectal Cancer Cells HCT116 Through Downregulation of Ezrin

“…What's more, several studies have found that baicalein exerts antiinflammatory and anti-cancer effects in a broad spectrum of cancers [7].. For example, baicalein can induce apoptosis and inhibit metastasis of prostate cancer cells through inactivation of the caveolin-1/AKT/mTOR pathway [8]. Besides, it has been demonstrated that baicalein has efficient anticancer effects on hepatocellular carcinoma (HCC) to suppress cell growth and cell survival via the alteration of either microRNA [9] or mRNA expression profiles, the adjustment in the expression of CD24 included [10]. Beyond that, the activation of the AMPK/ULK1 pathway induced by baicalein is associated with a variety of human cancers [11].…”

MicroRNA-214-5p Inhibits the Invasion and Migration of Hepatocellular Carcinoma Cells by Targeting Wiskott-Aldrich Syndrome Like

“…After curative resection [3, 4], HCC frequently breaks out tumor recurrence and metastasis [5, 6]. Although much effort has been made, there are no effective therapeutic strategy to cure Hepatocellular carcinoma [7, 8]. Therefore, it is of great significance to identify the mechanism of migration and invasion and develop targeted therapeutics.…”