Search

Selenium (Se) is an essential trace element that has several functions in cellular processes related to cancer prevention. While the cancericidal effect of Se has been reported in liver cancer, the mechanism has not been clarified. MiR-29a has widely been reported as a tumor suppressor; however, it also acts as a carcinogenic agent by increasing cell invasion in human epithelial cancer cells and hepatoma cells. In a previous study, we found that miR-29a-3p is a Se-sensitive miRNA. However, its effect in the chicken hepatocellular carcinoma cell line (LMH) is still unknown. In the present study, we found that the expression of miR-29a-3p in LMH cells was decreased by Se supplementation and increased under Se-deficient conditions. Flow cytometry and CCK-8 results suggested that Se decreased LMH cell proliferation induced by miR-29a-3p overexpression. Transwell and gap-closure assays implied that Se mediated LMH cell invasion and migration by downregulating miR-29a-3p. Quantitative real-time polymerase chain reaction and Western blotting results suggested that Se mitigated miR-29a-3p overexpression-induced LMH cell proliferation by downregulating CDK2, cyclin-D1, CDK6, and cyclin-E1. We further demonstrated that collagen type IV alpha 2 (COL4A2) is a target gene of miR-29a-3p. COL4A2 activates the RhoA/ROCK pathway to promote LMH cell invasion and migration. In conclusion, Se mediated miR-29a-3p overexpression induced LMH cell invasion and migration by targeting COL4A2 to inactivate the RhoA/ROCK pathway.

Selenium (Se) deficiency induces typical clinical and pathological changes and causes various pathological responses at the molecular level in several different chicken organs; the kidney is one of the target organs of Se deficiency. To explore the mechanisms that underlie the effects of microRNA-33-3p (miR-33-3p) on Se deficiency-induced kidney apoptosis, 60 chickens were randomly divided into two groups (30 chickens per group). We found that Se deficiency increased the expression of miR-33-3p in the chicken kidney. A disintegrin and metalloprotease domain 10 (ADAM10) was verified to be a target of miR-33-3p in the chicken kidney. The overexpression of miR-33-3p decreased the expression levels of β-catenin, cyclinD1, T-cell factor (TCF), c-myc, survivin, and Bcl-2; it increased the expression levels of E-cadherin, Bak, Bax, and caspase-3; and it increased the number of chicken kidney cells in the G0/G1 phase. In addition, Se deficiency caused the ultrastructure of the kidney to develop apoptotic characteristics. The results of flow cytometry analysis and AO/EB staining showed that the number of apoptotic chicken kidney cells increased in the miR-33-3p mimic group. All these results suggest that Se deficiency-induced cell cycle arrest and apoptosis in vivo and in vitro in the chicken kidney via the regulation of miR-33-3p, which targets ADAM10., (© 2019 Wiley Periodicals, Inc.)

Selenium (Se) is a type of nutrient element. The tissues of organisms can have pathological damage, including apoptosis, due to Se deficiency. Apoptosis is an important cell process and plays a key role in vascular disease and Se-deficient symptoms. In this study, the Se-deficient broiler model was duplicated, miR-33-3p in the vein was overexpressed in response to Se-deficiency, and miR-33-3p target gene E4F transcription factor 1 (E4F1) expression was also confirmed. We utilized ectopic miR-33-3p expression to validate its function for apoptosis. The results showed that miR-33-3p-targeted E4F1 are involved in the glucose-regulated protein 78- (GRP78-) induced endoplasmic reticulum stress (ERS) apoptosis pathway. We presumed that Se deficiency might trigger apoptosis via downregulating miR-33-3p. Interestingly, the miR-33-3p inhibitor and VER-155008 (GRP78 inhibitor) partly hindered the apoptosis caused by Se deficiency. Thus, the above information provides a new avenue toward understanding the mechanism of Se deficiency and reveals a novel apoptotic injury regulation model in vascular disease.

Apoptosis is a common paradigm of cell death and plays a key role in cartilage damage and selenium (Se) deficiency. Selenoproteins play major roles in determining the biological effects of Se, and are potentially involved in the pathophysiological processes in bone tissue. MicroRNAs (miRNAs) play important roles in cell proliferation, differentiation, apoptosis and tumorigenesis. Based on the preliminary results, the expression of selenoprotein M (SelM) was significantly decreased (69%) in chicken cartilage tissues with Se deficiency, and we subsequently screened and verified that SelM is one of the target genes of miR-138-5p in chicken cartilage using a dual luciferase reporter assay and real-time quantitative PCR (qRT-PCR). The expression of miR-138-5p was increased in response to Se deficiency, and the overexpression of miR-138-5p increased caspase-3, caspase-9, BAX and BAK levels, while the BCL-2 level was decreased, suggesting that miR-138-5p induced apoptosis via the mitochondrial pathway in vivo and in vitro. We explored whether oxidative stress, mitochondrial fission and fusion, and energy metabolism might trigger apoptosis to obtain an understanding of the mechanisms underlying the effects of miR-138-5p on Se deficiency-induced apoptosis in cartilage. The levels of indicators of oxidative stress, mitochondrial dynamics and energy metabolism were changed as well. This study confirmed that SelM is one of the target genes of miR-138-5p, and the overexpression of miR-138-5p induced by Se deficiency triggered oxidative stress, an imbalance in mitochondrial fission and fusion, and energy metabolism dysfunction. Therefore, miR-138-5p is involved in the mitochondrial apoptosis pathway via targeting SelM in chicken chondrocytes.

Vein endothelial cells (VECs) constitute an important barrier for macromolecules and circulating cells from the blood to the tissues, stabilizing the colloid osmotic pressure of the blood, regulating the vascular tone, and rapidly changing the intercellular connection, and maintaining normal physiological function. Tight junction has been discovered as an important structural basis of intercellular connection and may play a key role in intercellular connection injuries or vascular diseases and selenium (Se) deficiency symptoms. Hence, we replicated the Se-deficient broilers model and detected the specific microRNA in response to Se-deficient vein by using quantitative real time-PCR (qRT-PCR) analysis. Also, we selected miR-128-1-5p based on differential expression in vein tissue and confirmed its target gene cell adhesion molecule 1 (CADM1) by the dual luciferase reporter assay and qRT-PCR in VECs. We made the ectopic miR-128-1-5p expression for the purpose of validating its function on tight junction. The result showed that miR-128-1-5p and CADM1 were involved in the ZO-1-mediated tight junction, increased paracellular permeability, and arrested cell cycle. We presumed that miR-128-1-5p and Se deficiency might trigger tight junction. Interestingly, miR-128-1-5p inhibitor and fasudil in part hinder the destruction of the intercellular structure caused by Se deficiency. The miR-128-1-5p/CADM1/tight junction axis provides a new avenue toward understanding the mechanism of Se deficiency, revealing a novel regulation model of tight junction injury in vascular diseases., (© 2018 Wiley Periodicals, Inc.)