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Aldehyde dehydrogenase 1, a target of miR-222, is expressed at elevated levels in cervical cancer.

ABSTRACT: The aim of the present study was to investigate the expression of microRNA-222 (miR-222) and aldehyde dehydrogenase 1 (ALDH1) in tissues and peripheral blood of cervical cancer patients, and to elucidate their underlying mechanisms of action. Tumor tissues and tumor-adjacent tissues were obtained from 33 cervical cancer patients and peripheral blood was obtained from these patients and 28 healthy subjects. The expression of miR-222 and ALDH1 mRNA was evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). To examine the levels of ALDH1 protein in tissues and blood, western blotting and ELISA were used. To confirm a direct interaction between miR-222 and ALDH1 mRNA, a dual luciferase reporter assay was performed. HeLA cells were transfected with agomiR-222 and expression of ALDH1 in the cells was measured by RT-qPCR and western blotting. MTT assay was preform to investigate the proliferation of HeLA cells. Expression of ALDH1 mRNA and protein was elevated in cervical cancer tissues and peripheral blood from patients compared with tumor-adjacent tissues and healthy controls, while the expression of miR-222 was reduced. Upregulation of miR-222 inhibited HeLA cell proliferation possibly due to a reduction in the expression of ALDH1. A dual luciferase reporter assay showed that miR-222 can bind with the 3'-untranslated seed region of ALDH1 mRNA to regulate its expression. miR-222 regulation of ALDH1 expression may play a role in the prevention of cervical cancer.

SUBMITTER: Liu C

PROVIDER: S-EPMC7027150 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Aldehyde dehydrogenase 1, a target of miR-222, is expressed at elevated levels in cervical cancer.

Liu Changde C Zhang Yan Y Liang Shanghua S Ying Yuhua Y

Experimental and therapeutic medicine 20200107 3

The aim of the present study was to investigate the expression of microRNA-222 (miR-222) and aldehyde dehydrogenase 1 (ALDH1) in tissues and peripheral blood of cervical cancer patients, and to elucidate their underlying mechanisms of action. Tumor tissues and tumor-adjacent tissues were obtained from 33 cervical cancer patients and peripheral blood was obtained from these patients and 28 healthy subjects. The expression of miR-222 and ALDH1 mRNA was evaluated by reverse transcription-quantitati ...[more]

PMID: 32104219

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Project description:Aim: MicroRNA-222 (miR-222) and miR-29c have been identified as important modulators of cardiac growth and may protect against pathological cardiac remodeling. miR-222 and -29c may thus serve as functional biomarkers for exercise-induced cardiac adaptations. This investigation compared the effect of two workload-matched high-intensity interval training (HIIT) protocols with different recovery periods on miR-222 and -29c levels. Methods: Sixty-three moderately trained females and males (22.0 ± 1.7 years) fulfilled the eligibility criteria and were randomized into two HIIT groups using sex and exercise capacity. During a controlled 4-week intervention (two sessions/week) a 4 × 30 HIIT group performed 4 × 30 s runs (all-out, 30 s active recovery) and a 8 × 15 HIIT group performed 8 × 15 s runs (all-out, 15 s active recovery). miR-222 and -29c as well as transforming growth factor-beta1 (TGF-beta1) mRNA levels were determined during high-intensity running as well as aerobic exercise using capillary blood from earlobes. Performance parameters were assessed using an incremental continuous running test (ICRT) protocol with blood lactate diagnostic and heart rate (HR) monitoring to determine HR recovery and power output at individual anaerobic threshold (IAT). Results: At baseline, acute exercise miR-222 and -29c levels were increased only in the 4 × 30 HIIT group (both p < 0.01, pre- vs. post-exercise). After the intervention, acute exercise miR-222 levels were still increased in the 4 × 30 HIIT group (p < 0.01, pre- vs. post-exercise) while in the 8 × 15 HIIT group again no acute effect was observed. However, both HIIT interventions resulted in elevated resting miR-222 and -29c levels (all p < 0.001, pre- vs. post-intervention). Neither of the two miRNAs were elevated at any ICRT speed level at baseline nor follow-up. While HR recovery was improved by >24% in both HIIT groups (both p ? 0.0002) speed at IAT was improved by 3.6% only in the 4 × 30 HIIT group (p < 0.0132). Correlation analysis suggested an association between both miRNAs and TGF-beta1 mRNA (all p ? 0.006, r ? 0.74) as well as change in speed at IAT and change in miR-222 levels (p = 0.024, r = 0.46). Conclusions: HIIT can induce increased circulating levels of cardiac growth-associated miR-222 and -29c. miR-222 and miR-29c could be useful markers to monitor HIIT response in general and to identify optimal work/rest combinations.

Project description:BackgroundmiR-21, miR-26b, miR-221/222 and miR-126 play crucial roles in cervical cancer development. Studies have shown that polymorphisms in miRNA genes can affect miRNA expression, which might be associated with cancer development.MethodsTen single-nucleotide polymorphisms (SNPs) in the miR-21, miR-26b, miR-221/222 and miR-126 genes (rs1292037, rs13137 in miR-21; rs2227255, rs2227258 in miR-26b; rs2858061, rs34678647, rs2858060, rs2745709 in miR-221/222; rs2297537, rs2297538 in miR-126) were selected, and genotyped in a total of 2176 individuals, including 435 patients with cervical intraepithelial neoplasia (CIN), 743 patients with cervical cancer (CC) and 998 healthy persons using TaqMan assays, and their associations with CIN and CC were evaluated.ResultsOur results showed significant differences for the rs2297538 genotypes between the CIN and CC groups (P = 0.001). In addition, our results also showed significant differences for the rs2297537 alleles between the CIN and CC groups (P = 0.003), and the C allele of rs2297537 might be associated with a decreased risk of CC (OR = 0.72, 95%CI: 0.58-0.90). At the inheritance analysis, between the CIN and control groups, the T/T-T/C genotype in rs1292037 and A/A-A/T genotype in rs13137 might be associated with an increased risk of CIN in the recessive model (OR = 1.61, 95% CI: 1.17-2.20 and OR = 1.58, 95% CI: 1.15-2.15). In addition, the C/C-T/T genotype of rs2745709 might be associated with a decreased risk of CIN in the overdominant model (OR = 0.66, 95% CI: 0.52-0.82). Between, CIN and CC group, the T/T-C/C genotype in rs1292037 and A/A-T/T genotype in rs13137 might be associated with an increased risk of CC in the overdominant model (OR = 1.43, 95% CI: 1.12-1.81 and OR = 1.42, 95% CI: 1.12-1.80). The rs2297538 G/G-A/G genotype might be associated with an increased risk of CC in the recessive model (OR = 2.83, 95% CI: 1.52-5.25). The rs2297537 2C/C + C/G genotype might be associated with a decreased risk of CC (OR = 0.71, 95% CI: 0.57-0.89) in the log-additive model. The rs2745709 T/T-C/C genotype might be associated with an increased risk of CC (OR = 1.44, 95% CI: 1.13-1.83) in the overdominant model.ConclusionOur results indicate that rs2297538 and rs2297537 in miR-126, rs1292037 and rs13137 in miR-21, and rs2745709 in miR-221/222, may have important roles in the development of CIN or CC.

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Aldehyde dehydrogenase 1, a target of miR-222, is expressed at elevated levels in cervical cancer.

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Aldehyde dehydrogenase 1, a target of miR-222, is expressed at elevated levels in cervical cancer.

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