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Cancer Cell International
Published in: Cancer Cell International 1/2020

Open Access 01-12-2020 | Pancreatic Cancer | Primary research

Silencing of microRNA-135b inhibits invasion, migration, and stemness of CD24+CD44+ pancreatic cancer stem cells through JADE-1-dependent AKT/mTOR pathway

Authors: Jingyang Zhou, Haihong Wang, Jinhui Che, Lu Xu, Weizhong Yang, Yunjiu Li, Wuyuan Zhou

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

Recent studies have emphasized determining the ability of microRNAs (miRNAs) as crucial regulators in the occurrence and development of pancreatic cancer (PC), which continues to be one of the deadliest malignancies with few effective therapies. The study aimed to investigate the functional role of miR-135b and its associated mechanism to unravel the biological characteristics of tumor growth in pancreatic cancer stem cells (PCSCs).

Methods

Microarray analyses were initially performed to identify the PC-related miRNAs and genes. The expression of miR-135b and PCSC markers in PC tissues and cells was determined by RT-qPCR and western blot analysis, respectively. The potential gene (JADE-1) that could bind to miR-135b was confirmed by the dual-luciferase reporter assay. To investigate the tumorigenicity, migration, invasion, and stemness of PC cells, several gain-of-function and loss-of-function genetic experiments were conducted. Finally, tumor formation in nude mice was conducted to confirm the results in vivo.

Results

miR-135b was highly-expressed in PC tissues and PCSCs, which was identified to specifically target JADE-1. The overexpression of miR-135b promoted proliferation, migration, and invasion of PCSC, inhibited cell apoptosis and increased the expression of stemness-related factors (Sox-2, Oct-4, Nanog, Aldh1, and Slug). Moreover, miR-135b could promote the expression of phosphorylated AKT and phosphorylated mTOR in the AKT/mTOR pathway. Additionally, miR-135b overexpression accelerated tumor growth in nude mice.

Conclusions

Taken together, the silencing of miR-135b promotes the JADE-1 expression, which inactivates the AKT/mTOR pathway and ultimately results in inhibition of self-renewal and tumor growth of PCSCs. Hence, this study contributes to understanding the role of miR-135 in PCSCs and its underlying molecular mechanisms to aid in the development of effective PC therapeutics.
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Metadata
Title
Silencing of microRNA-135b inhibits invasion, migration, and stemness of CD24+CD44+ pancreatic cancer stem cells through JADE-1-dependent AKT/mTOR pathway
Authors
Jingyang Zhou
Haihong Wang
Jinhui Che
Lu Xu
Weizhong Yang
Yunjiu Li
Wuyuan Zhou
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01210-1

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