LncRNA SAMMSON Overexpression Suppresses Vascular Smooth Muscle Cell Proliferation via Inhibiting miR-130a Maturation to Participate in Intracranial Aneurysm

Abstract

Background MiR-130a is a recently identified critical player in vascular smooth muscle cell (VSMC) proliferation, which participates in intracranial aneurysm (IA). However, the involvement of miR-130a in IA and its upstream regulator are unknown. Our preliminary sequencing analysis revealed a close correlation between miR-130a and lncRNA SAMMSON across IA samples. Therefore, we further studied the crosstalk between SAMMSON and miR-130a in IA. Methods SAMMSON and miR-130a expression were measured using RT-qPCR. SAMMSON subcellular location was analyzed with nuclear fractionation assay. Their direct interaction was explored with RNA pull-down assay. The role of SAMMSON in miR-130a maturation was studied with overexpression analysis. VSMC cell proliferation was analyzed with BrdU assay. Results SAMMSON and premature miR-130a were deregulated in IA, while mature miR-130a was upregulated in IA. SAMMSON is localized in both the nucleus and cytoplasm, and direct interaction between SAMMSON and miR-130a was observed. SAMMSON overexpression suppressed miR-130a maturation in VSMCs and reduced the enhancing effects of miR-130a on VSMC cell proliferation. Conclusion SAMMSON is overexpressed in IA and suppresses VSMC proliferation via inhibiting miR-130a maturation.

The oncogenic role of SAMMSON lncRNA in tumorigenesis: A comprehensive review with especial focus on melanoma

“…Generally, SAMMSON is remarkably upregulated in cancer; however Pan et al reported that the expression level of SAMMSON was decreased in intracranial aneurysm 14 . SAMMSON appears to have an impact on a variety of processes, including the regulation of mitochondrial function, cell proliferation, apoptosis, EMT, drug resistance, invasion and migration.…”

“…SAMMSON is located on the 3p13 chromosome and exists 4 exons and 28 transcripts that are produced through alternative splicing (https://asia.ensembl.org/Homo_sapiens/Gene/Splice?db=core;g=ENSG00000240405;r=3:69999550-70518064). Upregulation of SAMMSON was observed in several cancers, including melanoma, 10 breast cancer, 11 glioblastoma 12 and liver cancer 13 ; also, SAMMSON played a critical role in intracranial aneurysms 14 . Past studies reveal that approximately 10% of melanoma patients involved focal amplifications of chromosome 3p13–3p14.…”

Circulating miR-130a-3p is elevated in patients with cerebral atherosclerosis and predicts 2-year risk of cerebrovascular events

“…For example, in an AS mice model, miR-377-3p could suppress vascular smooth muscle cell proliferation and migration, which was considered as a potential mechanism of miR-377-3p involving in AS pathogenesis [ 16 ]. As a functional miRNA, miR-130a-3p has also been reported to modulate the cell viability and migration of vascular smooth muscle cells [ 12 , 13 ]. In our study, we found that serum miR-130a-3p was significantly elevated in cerebral AS patients compared with controls, indicating the potential role of miR-130a-3p in AS pathogenesis.…”

“…miR-130a-3p has been investigated in patients with carotid stenosis, and it was found to be elevated in stenosis progression [ 11 ]. In addition, miR-130a-3p has regulatory effects on the cell proliferation and migration of vascular smooth muscle cells, which are the critical pathomechanisms of AS [ 12 , 13 ]. These previous findings indicated that there may be some relationship between miR-130a-3p and cerebral AS.…”

Bioinformatics analysis constructs potential ferroptosis-related ceRNA network involved in the formation of intracranial aneurysm

“…The lncRNAs are more than 200 nucleotides in length but do not have protein-coding capacity ( Wilusz, 2016 ). The aberrant expression of lncRNAs in IA suggests a possible role in its pathogenesis, and various studies have reported the importance of lncRNAs in IA ( Li et al, 2020 ; Pan W. et al, 2021 ; Pan Y. B. et al, 2021 ).…”