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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Long non-coding RNA SNHG16 promotes human placenta-derived mesenchymal stem cell proliferation capacity through the PI3K/AKT pathway under hypoxia
Xu-Dong Feng, Jia-Hang Zhou, Jun-Yao Chen, Bing Feng, Rui-Tian Hu, Jian Wu, Qiao-Ling Pan, Jin-Feng Yang, Jiong Yu, Hong-Cui Cao
Xu-Dong Feng, Jia-Hang Zhou, Jun-Yao Chen, Bing Feng, Jian Wu, Qiao-Ling Pan, Jin-Feng Yang, Jiong Yu, Hong-Cui Cao, State Key Laboratory for The Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
Rui-Tian Hu, Department of Chemistry, Duke University, Durham, NC 27708, United States
Jian Wu, Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, Shandong Province, China
Hong-Cui Cao, Key Laboratory of Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
Author contributions: Feng XD contributed to the study design, experiments, data collection, and manuscript writing; Zhou JH, Chen JY, Feng B, Hu RT, and Wu J contributed to data collection and analysis; Pan QL, Yang JF and Yu J contributed to revising the manuscript; Cao HC contributed to design of the study, revision of the manuscript, and funding acquisition; All authors have read and approved the final manuscript.
Supported by Stem Cell and Translational Research from National Key Research and Development Program of China, No. 2020YFA0113003; and National Natural Science Foundation of China, No. 81971756.
Institutional review board statement: All protocols for the processing of human tissues and cells were approved by the Ethics Committee of The First Affiliated Hospital of Zhejiang University, No. 2020-1088.
Informed consent statement: Informed consent was waived.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data presented in this study are available within the article text and figures.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Hong-Cui Cao, Professor, State Key Laboratory for The Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China.
hccao@zju.edu.cn
Received: May 2, 2022
Peer-review started: May 2, 2022
First decision: June 11, 2022
Revised: June 24, 2022
Accepted: August 15, 2022
Article in press: August 15, 2022
Published online: September 26, 2022
Processing time: 143 Days and 21.5 Hours
ARTICLE HIGHLIGHTS
Research background
As the role of hypoxia on mesenchymal stem cells (MSCs) is an emerging topic of MSCs biology, increasing studies are devoted to researching the regulation mechanisms of hypoxia on the biological functions of MSCs. Long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) are reported to possess a critical role in regulating MSC biological characteristics. Nonetheless, the specific expression and co-expressed profiles of lncRNAs and mRNAs in human placenta-derived MSCs (hP-MSCs) under hypoxia and underlying mechanism of lncRNAs on hP-MSCs biology are still unknown.
Research motivation
Although some studies have explored the effects of hypoxia on MSCs, the role of lncRNAs in them remains unclear.
Research objectives
In this study, we aimed to reveal the specific expression profiles of lncRNAs in hP-MSCs under hypoxia and initially explored the possible mechanism of lncRNAs on hP-MSCs biology.
Research methods
Here, we used a multigas incubator (92.5% N2, 5%CO2 and 2.5% O2) to mimic a hypoxia condition and observed that hypoxic culture can significantly promote the proliferation potential of hP-MSCs. RNA sequencing technology was applied to identify the exact expression profiles of lncRNAs and mRNAs under hypoxia. After establishment of SNHG16-knockdown and SNHG16-overexpression hP-MSCs, the effect of SNHG16 on proliferation capacity of hP-MSCs was analyzed via cell counting kit-8 and cell cycle analysis. Finally, the underlying mechanism was analyzed by western blot.
Research results
We identified 289 differentially expressed lncRNAs and 240 differentially expressed mRNAs between hypoxia group and normoxia group. Among them, the lncRNA SNHG16 was upregulated under hypoxia, which was also validated by reverse transcription polymerase chain reaction. SNHG16 was confirmed to affect hP-MSCs proliferation rates by studying the SNHG16 knockdown model. SNHG16 overexpression could significantly enhance proliferation capacity of hP-MSCs, activate PI3K/AKT pathway, and upregulate the expression of cell cycle-related proteins.
Research conclusions
Our results revealed the specific expression characteristics of lncRNAs and mRNAs in hypoxia-cultured hP-MSCs and identified that hypoxia-responsive lncRNA SNHG16 can promote hP-MSC proliferation through the PI3K/AKT pathway.
Research perspectives
This study may contribute to understanding the role of noncoding RNAs in MSC biology.
