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. 2023;42(1):87-93.
doi: 10.12938/bmfh.2022-056. Epub 2022 Oct 5.

Quercetin up-regulates the expression of tumor-suppressive microRNAs in human cervical cancer

Motoki Murata  1   2 , Satomi Komatsu  1 , Emi Miyamoto  1 , Chihiro Oka  1 , Ichian Lin  1 , Motofumi Kumazoe  1 , Shuya Yamashita  1 , Yoshinori Fujimura  1 , Hirofumi Tachibana  1
Affiliations

Quercetin up-regulates the expression of tumor-suppressive microRNAs in human cervical cancer

Motoki Murata et al. Biosci Microbiota Food Health. 2023.

Abstract

Quercetin, a flavonol present in many vegetables and fruits, has been identified as a chemoprevention agent in several cancer models. However, the molecular mechanism of quercetin's anticancer activity is not entirely understood. MicroRNAs (miRNAs), small noncoding RNAs, have been reported to play key roles in various biological processes by regulating their target genes. We hypothesized that quercetin can exert an anticancer effect through the regulation of miRNAs. To test this hypothesis, we investigated the effects of quercetin on the expression of tumor-suppressive miRNAs in cervical cancer. Quercetin up-regulated the in vivo and in vitro expression of tumor-suppressive miRNAs miR-26b, miR-126, and miR-320a. Quercetin suppressed the level of β-catenin, encoded by catenin beta 1 (CTNNB1), by up-regulating miR-320a in HeLa cells. Moreover, quercetin increased the expression of mir-26b, mir-126, and mir-320a precursors in HeLa cells. The results from this study show that quercetin has the potential to prevent cervical cancer by regulating the expression of tumor-suppressive miRNAs.

Keywords: cervical cancer; microRNA; quercetin; β-catenin.

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Figures

Fig. 1.
Fig. 1.
Dietary quercetin up-regulates tumor-suppressive microRNA (miRNA) expression in uterine cervical tumors. (A, B) Nude mice implanted with HeLa cells. After the formation of tumors, mice were administered quercetin orally (10 or 50 mg/kg b.w./2 days). Eleven days after administration, miRNA expression was measured in the uterine cervix tumors. Results represent means ± SEM (n = 6–10). Asterisks indicate statistical significance to 0 mg/kg b.w. quercetin treatment calculated. *p<0.05. (C) C57BL/6J mice were administered quercetin orally (50 mg/kg b.w.). At 48 hr after administration, the expression of miR-26b, miR-126, and miR-320 was measured in plasma. Results represent means ± SEM (n=6).
Fig. 2.
Fig. 2.
Quercetin up-regulates tumor-suppressive microRNA (miRNA) expression in cervical cancer cells. HeLa cells were treated with the indicated concentrations of quercetin for 24 hr, and then miRNA expression was measured by qRT-PCR. Results represent means ± SEM from three independent experiments (n=3). Asterisks indicate statistical significance to 0 μM quercetin treatment calculated. *p<0.05; **p<0.01.
Fig. 3.
Fig. 3.
Quercetin suppresses the β-catenin level by modulating miR-320a activities. (A) β-catenin level in HeLa cells treated with quercetin for 72 hr. (B) The β-catenin level was measured when HeLa cells were transfected with 10 nM miR-320a inhibitor for 48 hr and then treated with 5 μM quercetin for 72 hr. Results represent means ± SEM from three independent experiments (n=3). Asterisks indicate statistical significance to 0 μM quercetin treatment calculated. *p<0.05; **p<0.01.
Fig. 4.
Fig. 4.
Quercetin promotes tumor-suppressive microRNA (miRNA) precursor expression. HeLa cells were treated with 5 μM quercetin for 0–24 hr, and then precursor miRNA (pre-mir-26b, pre-mir-126, and pre-mir-320a) expression was measured by qRT-PCR. Results represent means ± SEM from four independent experiments (n=4). Asterisks indicate statistical significance to quercetin 0 hr treatment calculated. *p<0.05; **p<0.01.
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