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A positive feedback loop between AlkB homolog 5 and miR-193a-3p promotes growth and metastasis in esophageal squamous cell carcinoma

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Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignancies worldwide. miR-193a-3p acts as an oncogene or tumor suppressor in different cancers. However, the functional role and regulatory mechanism of miR-193a-3p in ESCC remain to be elucidated. Our results demonstrated that miR-193a-3p expression was significantly upregulated and associated with advanced TNM stage, recurrence, and poor prognosis in ESCC patients. miR-193-3p targeted ALKBH5 and suppressed its expression. ALKBH5 inhibited miR-193a-3p expression in turn. ALKBH5 affected the primary miR-193a-3p processing by negatively regulating its m6A modification. These findings suggested a positive feedback regulation between miR-193a-3p and ALKBH5 in ESCC cells. Moreover, the functional assays indicated that the miR-193-3p-ALKBH5 feedback loop promoted the proliferation, migration and invasion ability of ESCC cells in vitro, and facilitated tumor growth and metastasis in vivo. Collectively, our current study identified a novel positive feedback regulation between miR-193a-3p and ALKBH5 in ESCC, which may be helpful to gain insight into ESCC pathogenesis and provide novel therapeutic target for ESCC.

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Availability of data and materials

The data and materials used in this study are available.

Abbreviations

EC:

Esophageal cancer

ESCC:

Esophageal squamous cell carcinoma

miRNAs:

MicroRNAs

3′UTR:

3′-Untranslated region

m6A:

N6-methyladenosine

METTL3:

Methyltransferase-like 3

ALKBH5:

AlkB homolog 5

FTO:

Fat mass and obesity–associated protein

MeRIP:

Methylated RNA immunoprecipitation

qRT-PCR:

Quantitative Real-time PCR

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Acknowledgements

The study was supported by Natural Science Fund of Luoyang Central Hospital Affiliated to Zhengzhou University.

Funding

The study was supported by Natural Science Fund of Luoyang Central Hospital Affiliated to Zhengzhou University.

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Authors and Affiliations

  1. Department of Thoracic Surgery, Luoyang Central Hospital Affiliated To Zhengzhou University, No.288, Zhongzhou Middle Road, Luoyang City, 471009, Henan Province, China

    Jinliang Xue, Peng Xiao, Xiangdong Yu & Xiao Zhang

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  1. Jinliang Xue
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  2. Peng Xiao
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  3. Xiangdong Yu
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  4. Xiao Zhang
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Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

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Correspondence to Xiao Zhang.

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Conflict of interest

All the authors declare that they have no competing financial interests.

Ethical approval

The Ethics Committee of the Luoyang Central Hospital Affiliated to Zhengzhou University approved the study protocols and the use of these tissue samples (approval number: 201908–06) in accordance with the Declaration of Helsinki. The animal studies were approved by the Institutional Animal Care and Use Committee of the Luoyang Central Hospital Affiliated to Zhengzhou University.

Informed consent

The informed consent was obtained from all patients in this research. The protocol of this study was approved by the Ethics Committee of Luoyang Central Hospital Affiliated to Zhengzhou University and carried out in accordance with the World Medical Association Declaration of Helsinki.

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Not applicable.

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Electronic supplementary material

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13577_2020_458_MOESM1_ESM.tif

Supplemental Figure 1 FTO does not affect miR-193a-3p expression. A. KYSE-150 and ECA109 cells were transfected with negative control or FTO siRNAs, and the FTO mRNA expression was detected by qRT-PCR. B. KYSE-150 and ECA109 cells were transfected with negative control or FTO siRNAs, and the miR-193a-3p expression was detected by qRT-PCR. **p<0.01. (TIF 1102 KB)

13577_2020_458_MOESM2_ESM.tif

Supplemental Figure The knockdown efficacy of siRNA against METTL3, METTL14 or WTAP in ESCC cells was determined by qRT-PCR (TIF 1198 KB)

13577_2020_458_MOESM3_ESM.jpg

Supplemental Figure 3 The correlation between ALKBH5 and prognosis of Esophageal carcinoma patients from TCGA database was analyzed GEPIA online tool (JPG 55 KB)

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Xue, J., Xiao, P., Yu, X. et al. A positive feedback loop between AlkB homolog 5 and miR-193a-3p promotes growth and metastasis in esophageal squamous cell carcinoma. Human Cell 34, 502–514 (2021). https://doi.org/10.1007/s13577-020-00458-z

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  • DOI: https://doi.org/10.1007/s13577-020-00458-z

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