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FTO Knockdown-Mediated Maturation of miR-383-5p Inhibits Malignant Advancement of Pancreatic Cancer by Targeting ITGA3

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Abstract

m6A demethylase FTO is confirmed to be involved in pancreatic cancer progression. FTO regulates miRNA processing. To investigate the regulatory effect of FTO on miR-383-5p and its role in pancreatic cancer. The expression of miR-383-5p, ITGA3, and FTO was predicted using bioinformatic analysis in tissues and was measured using qPCR in cells. Cell biological functions were investigated using MTT assay, Transwell assay, sphere formation assay, and qPCR. The targeting relationship between miR-383-5p and ITGA3 was evaluated using the dual-luciferase reporter assay. The effect of FTO on miR-383-5p processing was evaluated using RIP and MeRIP assay. FTO expression was upregulated in pancreatic cancer and silencing of FTO promoted the processing of miR-383-5p in an m6A-dependent manner. m6A-modified miRNA processing was recognized by IGF2BP1. Downregulation of miR-383-5p reversed FTO knockdown-induced inhibition of cellular processes. The FTO/miR-383-5p/ITGA3 axis facilitated cell viability, metastasis, and stemness in pancreatic cancer.

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Availability of Data and Materials

The datasets used or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

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Funding

This study was supported by Research Project of Shanghai Municipal Health Commission (Youth) / 20204Y0169.

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Authors and Affiliations

  1. Department of Radiology, Children’s Hospital of Nanjing Medical University, No. 72, Guangzhou Road, Gulou District, Nanjing, 210008, China

    Wei Zhang

  2. Department of Interventional and Vascular Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, No. 301, Yanchang Road, Jing’an District, Shanghai, 200072, China

    Shilong Han, Yifeng Yuan & Minjie Xu

  3. AnHui University of Science and Technology, No. 168, Taifeng Road, Huainan, 232001, Anhui, China

    Anle Ding

  4. Department of Interventional and Vascular Surgery, Shanghai Tenth People’s Hospital, School of Clinical Medicine of Nanjing Medical University, No. 301, Yanchang Road, Jing’an District, Shanghai, 200072, China

    Maoquan Li

Authors
  1. Wei Zhang
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  2. Shilong Han
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  3. Yifeng Yuan
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  4. Minjie Xu
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  5. Anle Ding
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  6. Maoquan Li
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Contributions

WZ, SH, YY, MX, AD and ML conceived the study; YY, MX and AD conducted the experiments; SH and ML analyzed the data; WZ wrote the manuscript; all the authors read and approved the final version of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Maoquan Li.

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Zhang, W., Han, S., Yuan, Y. et al. FTO Knockdown-Mediated Maturation of miR-383-5p Inhibits Malignant Advancement of Pancreatic Cancer by Targeting ITGA3. Biochem Genet (2023). https://doi.org/10.1007/s10528-023-10560-0

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