1. Academic Validation
  2. MiR-30c-5p loss-induced PELI1 accumulation regulates cell proliferation and migration via activating PI3K/AKT pathway in papillary thyroid carcinoma

MiR-30c-5p loss-induced PELI1 accumulation regulates cell proliferation and migration via activating PI3K/AKT pathway in papillary thyroid carcinoma

  • J Transl Med. 2022 Jan 6;20(1):20. doi: 10.1186/s12967-021-03226-1.
Tingting Zheng  # 1 Youxing Zhou 2 Xiaowei Xu 1 Xin Qi 3 Jiameng Liu 1 Yanan Pu 4 Shan Zhang 1 Xuerong Gao 1 Xinkai Luo 1 Mei Li 5 Xuefeng Wang 1 6 Liyang Dong 7 Ying Wang 8 Chaoming Mao 9
Affiliations

Affiliations

  • 1 Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, 212000, Jiangsu, People's Republic of China.
  • 2 Department of Surgery, Jiangyuan Hospital Affiliated To Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, Jiangsu, People's Republic of China.
  • 3 Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China.
  • 4 Department of Emergency Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China.
  • 5 Department of Pathology, The Affiliated Hospital of Jiangsu University, Zhenjiang, 212000, Jiangsu, People's Republic of China.
  • 6 Department of Central Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, 212000, Jiangsu, People's Republic of China.
  • 7 Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, 212000, Jiangsu, People's Republic of China. [email protected].
  • 8 Department of Respiratory Diseases, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, 223002, Jiangsu, People's Republic of China. [email protected].
  • 9 Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, 212000, Jiangsu, People's Republic of China. [email protected].
  • # Contributed equally.
Abstract

Background: The aberrant expression of E3 ubiquitin ligase Pellino-1 (PELI1) contributes to several human Cancer development and progression. However, its expression patterns and functional importance in papillary thyroid Cancer (PTC) remains unknown.

Methods: PELI1 expression profiles in PTC tissues were obtained and analyzed through the starBase v3.0 analysis. Real-Time PCR, Immunohistochemical assays (IHC) and Western blot were used to investigate the mRNA and protein levels of PELI1 in PTC. The effects of PELI1 on PTC cell progression were evaluated through CCK-8, colony formation, Transwell, and Wound healing assay in vitro, and a PTC xenograft mouse model in vivo. The downstream target signal of PELI1 in PTC was analyzed by using Kyoto encyclopedia of genes and genomes (KEGG), and bioinformatics tools were used to identify potential miRNAs targeting PELI1. Human umbilical cord mesenchymal stem cells were modified by miR-30c-5p and the miR-30c-5p containing extracellular vesicles were collected (miR-30c-5p-EVs) by ultra-high-speed centrifugation method. Then, the effects of miR-30c-5p-EVs on PELI1 expression and PTC progression were evaluated both in vitro and in vivo.

Results: Both mRNA and protein expression of PELI1 were widely increased in PTC tissues, and overexpression of PELI1 was positively correlated with bigger tumor size and lymph node metastases. PELI1 promoted PTC cell proliferation and migration in vitro. While, PELI1 silencing significantly suppressed PTC growth in vivo accompanied with reduced expression of Ki-67 and matrix metallopeptidase 2 (MMP-2). Mechanistically, PI3K-AKT pathway was identified as the downstream target of PELI1, and mediated the functional influence of PELI1 in PTC cells. Moreover, we found that the expression of miR-30c-5p was inversely correlated with PELI1 in PTC samples and further confirmed that miR-30c-5p was a tumor-suppressive miRNA that directly targeted PELI1 to inhibit PTC cell proliferation and migration. Furthermore, we showed that miR-30c-5p-EVs could effectively downregulate PELI1 expression and suppress the PTC cell growth in vitro and in vivo.

Conclusion: This study not only supported the first evidence that miR-30c-5p loss-induced PELI1 accumulation facilitated cell proliferation and migration by activating the PI3K-AKT pathway in PTC but also provided novel insights into PTC therapy based on miR-carrying-hUCMSC-EVs.

Keywords

PELI1; PI3K/AKT; Papillary thyroid carcinoma; hUCMSC-EVs; miR-30c-5p.

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