The effect of hypoxia on mesenchymal stem cells (MSCs) is an emerging topic in MSC biology. Although long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) are reported to play a critical role in regulating the biological characteristics of MSCs, their specific expression and co-expression profiles in human placenta-derived MSCs (hP-MSCs) under hypoxia and the underlying mechanisms of lncRNAs in hP-MSC biology are unknown.
To reveal the specific expression profiles of lncRNAs in hP-MSCs under hypoxia and initially explored the possible mechanism of lncRNAs on hP-MSC biology.
Here, we used a multigas incubator (92.5% N2, 5% CO2, and 2.5% O2) to mimic the hypoxia condition and observed that hypoxic culture significantly promoted the proliferation potential of hP-MSCs. RNA sequencing technology was applied to identify the exact expression profiles of lncRNAs and mRNAs under hypoxia.
We identified 289 differentially expressed lncRNAs and 240 differentially expressed mRNAs between the hypoxia and normoxia groups. 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-MSC proliferation rates using a SNHG16 knockdown model. SNHG16 overexpression could significantly enhance the proliferation capacity of hP-MSCs, activate the PI3K/AKT pathway, and upregulate the expression of cell cycle-related proteins.
Our results revealed the specific expression characteristics of lncRNAs and mRNAs in hypoxia-cultured hP-MSCs and that lncRNA SNHG16 can promote hP-MSC proliferation through the PI3K/AKT pathway.
Core Tip: This study revealed the specific expression and co-expressed profiles of long non-coding RNAs and messenger RNAs in human placenta-derived mesenchymal stem cells under hypoxia by RNA sequencing assays. Through the performance of a series of systemic bioinformatic analyses, the hypoxia-responsive long non-coding RNA SNHG16 that may play a role in proliferation was screened out. Furthermore, through the use of molecular biology experiments, SNHG16 was found to affect human placenta-derived mesenchymal stem cell proliferation rates and cell cycle progression by activating the PI3K/AKT pathway and upregulating the expression of the key cell cycle regulators.
- Citation: Feng XD, Zhou JH, Chen JY, Feng B, Hu RT, Wu J, Pan QL, Yang JF, Yu J, Cao HC. Long non-coding RNA SNHG16 promotes human placenta-derived mesenchymal stem cell proliferation capacity through the PI3K/AKT pathway under hypoxia. World J Stem Cells 2022; 14(9): 714-728
- URL: https://www.wjgnet.com/1948-0210/full/v14/i9/714.htm
- DOI: https://dx.doi.org/10.4252/wjsc.v14.i9.714