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Research Paper|Volume 12, Issue 20|pp 20127—20138

Long non-coding RNA DLEUI promotes papillary thyroid carcinoma progression by sponging miR-421 and increasing ROCK1 expression

Rui Li1, Taihu Wan2, Jie Qu3, Yang Yu4, Ruipeng Zheng5
  • 1Department of Thyroid Surgery, The First Hospital of Jilin University, Changchun 130021, P.R. China
  • 2Department of Division of Interventional Radiology, China-Japan Union Hospital of Jilin University, Changchun 130033, China
  • 3Department of VIP Unit, China-Japan Union Hospital of Jilin University, Changchun 130033, China
  • 4Department of General Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China
  • 5Department of Interventional Therapy, The First Hospital of Jilin University, Changchun 130021, P.R. China
* Equal contribution
Received: February 3, 2019Accepted: June 22, 2020Published: September 10, 2020
https://doi.org/10.18632/aging.103642

Copyright: © 2020 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

We investigated the role of long non-coding RNA DLEU1 (deleted in lymphocytic leukemia 1) in the progression of papillary thyroid carcinoma (PTC). DLEU1 levels were higher in PTC cell lines (BHP5-16, TPC-1,8505C, and SW1736) and patient tissues (n=54) than in a human thyroid follicular epithelial cell line (Nthy-ori3-1) or adjacent normal thyroid tissues. High DLEU1 expression correlated positively with lymph node metastasis and advanced clinical stages in PTC patients. Bioinformatics, dual luciferase reporter, and RNA pulldown assays confirmed that DLEU1 directly binds to miR-421. Moreover, bioinformatics and dual luciferase reporter assays showed that miR-421 directly binds to the 3’untranslated region of the rho-related coiled-coil kinase 1 (ROCK1) in TPC-1 cells. PTC patient tissues and cell lines showed high ROCK1 mRNA and protein levels as well as low miR-421 levels. CCK-8, flow cytometry, wound healing, and Transwell invasion assays demonstrated that DLEU1 silencing decreases TPC-1 cell proliferation, survival and progression, but they can be rescued by miR-421 knockdown or ROCK1 overexpression. DLEU1 knockdown in TPC-1 cells decreased in vivo xenograft tumor size and weight compared to controls in nude mice. These findings demonstrate that DLEU1 promotes PTC progression by sponging miR-421 and increasing ROCK1 expression.