LINC02015 modulates the cell proliferation and apoptosis of aortic vascular smooth muscle cells by transcriptional regulation and protein interaction network.
Fangyu LiuYulin WangXitong HuangDingqian LiuWenjun DingHao LaiChunsheng WangQiang JiPublished in: Cell death discovery (2023)
Long intergenic nonprotein coding RNA 2015 (LINC02015) is a long non-coding RNA that has been found elevated in various cell proliferation-related diseases. However, the functions and interactive mechanism of LINC02015 remain unknown. This study aimed to explore the role of LINC02015 in the cell proliferation and apoptosis of vascular smooth muscle cells (VSMCs) to explain the pathogenesis of aortic diseases. Ascending aorta samples and angiotensin-II (AT-II) treated primary human aortic VSMCs (HAVSMCs) were used to evaluate the LINC02015 expression. RNA sequencing, chromatin isolation by RNA purification sequencing, RNA pull-down, and mass spectrometry (MS) were applied to explore the potential interacting mechanisms. LINC02015 expression was found elevated in aortic dissection and AT-II-treated HAVSMCs. Cell proliferation and cell cycle were activated in HAVSMCs with LINC02015 knockdown. The cyclins family and caspase family were found to participate in regulating the cell cycle and apoptosis via the NF-κB signaling pathway. RXRA was discovered as a possible hub gene for LINC02015 transcriptional regulating networks. Besides, the protein interaction network of LINC02015 was revealed with candidate regulating molecules. It was concluded that the knockdown of LINC02015 could promote cell proliferation and inhibit the apoptosis of HAVSMCs through an RXRA-related transcriptional regulation network, which could provide a potential therapeutic target for aortic diseases.
Keyphrases
- cell proliferation
- cell cycle
- long non coding rna
- vascular smooth muscle cells
- poor prognosis
- angiotensin ii
- pi k akt
- aortic dissection
- cell cycle arrest
- signaling pathway
- mass spectrometry
- oxidative stress
- aortic valve
- endoplasmic reticulum stress
- long noncoding rna
- pulmonary artery
- cell death
- angiotensin converting enzyme
- gene expression
- induced apoptosis
- endothelial cells
- left ventricular
- pulmonary arterial hypertension
- genome wide
- dna damage
- dna methylation
- immune response
- transcription factor
- amino acid
- liquid chromatography
- copy number
- multiple sclerosis
- newly diagnosed
- tandem mass spectrometry
- nuclear factor