Apoptosis in HUVECs induced by microRNA‑616‑3p via X‑linked inhibitor of apoptosis protein targeting

Abstract

Atherosclerosis causes stroke and coronary heart disease and is associated with a high mortality rate worldwide. However, the pathogenesis of atherosclerosis remains unclear. Endothelial cell apoptosis is one of the early changes observed in atherosclerosis. Previous studies have found that microRNA (miR)-616-3p may be involved in the development of atherosclerosis, but the specific mechanism is not clear. The present study aimed to investigate whether miR-616-3p is involved in endothelial cell apoptosis and its underlying mechanism. The present study demonstrated that compared with normal HUVECs, HUVECs treated with oxidized low-density lipoprotein expressed higher miR-616-3p and lower X-linked inhibitor of apoptosis protein (XIAP) levels. In the present study, HUVECs were transfected with miR-616-3p mimic and Cell Counting Kit-8 (CCK-8), flow cytometry and TUNEL staining assays demonstrated that compared with miR-616-3p mimic control, the miR-616-3p mimic promoted HUVEC apoptosis. In addition, using StarBase 3.0 for bioinformatics analysis it was predicted that miR-616-3p may bind to the 3'untranslated region (UTR) of XIAP mRNA. The present study performed the CCK-8, flow cytometry, TUNEL staining and dual-luciferase reporter assays and demonstrated that miR-616-3p binds to the 3'UTR of the XIAP mRNA and inhibits its expression and that this further promotes apoptosis in HUVECs. In addition, western blotting demonstrated that compared with miR-616-3p mimic control, the miR-616-3p mimic increases the level of cleaved caspase-3 in HUVECs. In summary, the present study demonstrated that miR-616-3p can directly inhibit the expression of XIAP mRNA by targeting its 3'UTR which promoted apoptosis in HUVECs. miR-616-3p and XIAP may be used as therapeutic targets of atherosclerosis in the future.

PERK-mediated induction of miR-5p and miR-3p arms of miR-616 regulates cell growth by targeting c-MYC

“…However, our results show that miR-616 expression attenuates the Furthermore, we observed that expression of miR-616 was reduced in human breast cancers as compared to tumour adjacent normal tissue (Fig 9). In agreement with our results miR-616-3p has been shown to potentiate apoptosis in HUVECs (16), inhibit head and neck squamous cell carcinoma progression (17) and inhibit cell growth and mammosphere formation of breast cancer cells (18,25). Any small RNA having G-rich 6mer seed sequence (nt 2-7 of the guide strand) can reduce viability of cells when associated with RNA-induced silencing complex.…”

“…MiR-616 targets tissue factor pathway inhibitor (TFPI-2) in prostate cancer (9); PTEN in HCC and gastric cancer (15); SOX7 in glioma and NSCLC (14). However, miR-616-3p has been reported to reduce XIAP expression and potentiate apoptosis in HUVECs (16).…”

“…MiR-616 targets tissue factor pathway inhibitor (TFPI-2) in prostate cancer (9); PTEN in HCC and gastric cancer (15); SOX7 in glioma and NSCLC (14). However, miR-616-3p has been reported to reduce XIAP expression and potentiate apoptosis in HUVECs (16). LINC01614 promotes head and neck squamous cell carcinoma progression via PI3K/AKT signalling pathway and miR-616-3p can inhibit cancer progression by downregulating LINC01614 expression (17).…”

Hsa_circ_0015382 is involved in the pathogenesis of preeclampsia by mediating THBS2 expression

“…The tumor‐promoting impact of miR‐616‐3p had been reported in gastric cancer 17 and pancreatic cancer, 18 but it exerted an anti‐tumor impact on breast cancer 19 . Also, miR‐616‐3p could repress HUVEC proliferation and induce HUVEC apoptosis in atherosclerosis 20 . The former work showed that miR‐616‐3p could promote cell migration, growth and EMT via regulating tissue FPI‐2 in PE 21 .…”

“…19 Also, miR-616-3p could repress HUVEC proliferation and induce HUVEC apoptosis in atherosclerosis. 20 The former work showed that miR-616-3p could promote cell migration, growth and EMT via regulating tissue FPI-2 in PE. 21 However, the relationship between hsa_circ_0015382 and miR-616-3p in PE is unclear.…”