Identification of Long Noncoding RNAs Involved in Differentiation and Survival of Vascular Smooth Muscle Cells

Yeong-Hwan Lim; Juhee Ryu; Hyun Kook; Young-Kook Kim

doi:10.1016/j.omtn.2020.08.032

Identification of Long Noncoding RNAs Involved in Differentiation and Survival of Vascular Smooth Muscle Cells

Mol Ther Nucleic Acids. 2020 Aug 29:22:209-221. doi: 10.1016/j.omtn.2020.08.032. eCollection 2020 Dec 4.

Authors

Yeong-Hwan Lim^{1

2

3}, Juhee Ryu^{1

3

4}, Hyun Kook^{1

3

4}, Young-Kook Kim^{1

2

3}

Affiliations

¹ Basic Research Laboratory for Vascular Remodeling Research Laboratory, Chonnam National University Medical School, Jeollanam-do, Republic of Korea.
² Department of Biochemistry, Chonnam National University Medical School, Jeollanam-do, Republic of Korea.
³ Department of Biomedical Sciences, Center for Creative Biomedical Scientists at Chonnam National University, Jeollanam-do, Republic of Korea.
⁴ Department of Pharmacology, Chonnam National University Medical School, Jeollanam-do, Republic of Korea.

Abstract

Long noncoding RNAs (lncRNAs) have recently been implicated in many pathophysiological cardiovascular processes, including vascular remodeling and atherosclerosis. However, the functional role of lncRNAs in the differentiation, proliferation, and apoptosis of vascular smooth muscle cells (VSMCs) is largely unknown. In this study, differentially expressed lncRNAs in synthetic and contractile human VSMCs were screened using RNA sequencing. Among the seven selected lncRNAs, the expression of MSC-AS1, MBNL1-AS1, and GAS6-AS2 was upregulated, whereas the expression of NR2F1-AS1, FUT8-AS1, FOXC2-AS1, and CTD-2207P18.2 was reduced upon VSMC differentiation. We focused on the NR2F1-AS1 and FOXC2-AS1 lncRNAs and showed that their knockdown significantly reduced the expression of smooth muscle contractile marker genes (ACTA2, CNN1, and TAGLN). Furthermore, FOXC2-AS1 was found to regulate cell proliferation and apoptosis through Akt/mTOR signaling, and affect Notch signaling, which is a key regulator of the contractile phenotype of VSMCs. Taken together, we identified novel lncRNAs involved in VSMC proliferation and differentiation and FOXC2-AS1 as a multifunctional regulator for vascular homeostasis and associated diseases.

Keywords: FOXC2-AS1; NR2F1-AS1; differentiation; long noncoding RNAs; vascular smooth muscle cells.