Research Paper Volume 13, Issue 1 pp 241—261
In situ self-assembly of Au-antimiR-155 nanocomplexes mediates TLR3-dependent apoptosis in hepatocellular carcinoma cells
- 1 Department of Endocrinology, Shunde Hospital of Southern Medical University, The First People's Hospital of Shunde Foshan, Shunde 528300, P. R. China
- 2 State Key Laboratory of Bioelectronics, Chien-Shiung Wu Lab, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, P. R. China
- 3 Central Laboratory, Shunde Hospital of Southern Medical University, The First People's Hospital of Shunde Foshan, Shunde 528300, P. R. China
Received: January 29, 2020 Accepted: July 6, 2020 Published: November 5, 2020https://doi.org/10.18632/aging.103799
How to Cite
Copyright: © 2020 Yin 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.
MicroRNA 155 (miRNA-155) is frequently dysregulated in hepatocellular carcinoma (HCC) and other cancer types. Toll-like receptor 3 (TLR3), a putative miR-155 target, plays a key role in liver pathophysiology, and its downregulation in HCC cells is associated with apoptosis evasion and poor outcomes. Herein, we examined the ability of in situ self-assembled Au-antimiR-155 nanocomplexes (Au-antimiRNA NCs) to activate TLR3 signaling in HCC cells. Gene expression analysis confirmed an inverse relationship between miR-155 and TLR3 expression in HCC samples, and marked upregulation of miR-155 was observed in HCC cells but not in normal L02 hepatocytes. RNA immunoprecipitation confirmed physical interaction between miR-155 and TLR3, while negative regulation of TLR3 expression by miR-155 was demonstrated by luciferase reporter assays. Au-antimiR-155 NCs were self-assembled within HepG2 HCC cells, but not within control L02 cells. They efficiently silenced miR-155, thereby inhibiting proliferation and migration and inducing apoptosis in HepG2 cells. Molecular analyses suggested these effects are secondary to TLR3 signaling mediating NF-κB transcription, caspase-8 activation, and interleukin-1β (IL-1β) release. Our results provide a basis for future studies examining the in vivo applicability of this novel Au-antimiRNA NCs delivery system to halt HCC progression by activating pro-apoptotic TLR3 signaling.