WITHDRAWN: Yak FOXO1 and FOXO3 SNPs and association with production traits, and their promotes cells apoptosis via RNAi

Yak FOXO1 and FOXO3 SNPs and association with production traits, and their promotes cells apoptosis via RNAi.

Egg production is an economically important trait in poultry breeding and production. Follicular development was regulated by several hormones released and genes expressed in the granulosa cells, impacting the egg production and fecundity of hens. However, the molecular functions of these candidate genes that modulate these processes remain largely unknown. In the present study, bioinformatics analyses were performed to identify the candidate genes related to egg production in the ovarian tissue of White Leghorns with high egg production and Beijing You chicken with low egg production during sexual maturity and peak laying periods. The ovarian granulosa cells were used to assess the function of CYP21A1 by transfecting with CYP21A1-specific small interfering RNAs (siRNAs) and overexpression plasmids. We identified 514 differentially expressed genes (|Log2(fold change) | >1, P <0.05) between the 2 chicken breeds in both laying periods. Among these genes, CYP21A1, which is involved in the steroid hormone biosynthesis pathway was consistently upregulated in White Leghorns. Weighted gene co-expression network analysis (WGCNA) further suggested that CYP21A1 was a hub gene, which could positively respond to treatment with follicle stimulation hormone (FSH), affecting egg production. The interference of CYP21A1 significantly inhibited cell proliferation and promoted cell apoptosis. Overexpression of CYP21A1 promotes cell proliferation and inhibits cell apoptosis. Furthermore, the interference with CYP21A1 significantly downregulated the expression of STAR, CYP11A1, HSD3B1, and FSHR and also decreased the synthesis of progesterone (P4) and estradiol (E2) in granulosa cells. Overexpression of CYP21A1 increased the synthesis of P4 and estradiol E2 and the expression of steroid hormone synthesis-related genes in granulosa cells. Our findings provide new evidence for the biological role of CYP21A1 on granulosa cell proliferation, apoptosis, and steroid hormone synthesis, which lays the theoretical basis for improving egg production.

Long non-coding RNAs (lncRNAs) have been reported to play important roles in numerous kinds of cardiovascular disease, including chronic heart failure (CHF). In this study, we mainly focused on investigating the potential roles of lncRNA LUCAT1 patients with CHF. RT-PCR was used to detect the expressions of LUCAT1 and miR-612 in serum samples of CHF patients (n=60) and healthy volunteers. Relationships between the expressions of LUCAT1 and miR-612, LUCAT1 and overall survival (OS) were analyzed using the Kaplan-Meier method. Si-LUCAT1 and miR-612 mimic were constructed and respectively transfected into AC16 cells to explore the functions of LUCAT1 and miR-612. Cell proliferation abilities were detected by CCK-8 assay AC16 cells. Cell apoptotic rates were measured by flow cytometry (FACS) analysis. Western blot (WB) was performed to detect the protein levels of HOXA13, Bcl-2, Bax, Bad and Cleaved Caspase3. In addition, luciferase gene reporter assay was used to prove the relationships between LUCAT1 and miR-612, miR-612 and HOXA13. Firstly, we found that LUCAT1 was decreased for 1.7 folds in CHF patients, which was correlated with poor prognosis patients. LUCAT1 repression inhibited cell proliferation and promoted cell apoptosis in human cardiomyocyte cell line AC16 cells. Furthermore, we found that miR-612 was increased for 2.0 folds in CHF patients, which was negatively interacted with LUCAT1 expression. Luciferase gene reporter assay demonstrated that LUCAT1 could directly bind with miR-612 in AC16 cells. Moreover, miR-612 overexpression also inhibited cell proliferation and promoted cell apoptosis in AC16 cells. Luciferase reporter assay indicated that miR-612 could directly target at HOXA13 in AC16 cells, which was associated with cell proliferation and apoptosis. Finally, miR-612 inhibitor was transfected into AC16 cells with si-LUCAT1. The results showed that the inhibited cell proliferation and promoted cell apoptosis were reversed, which confirmed that LUCAT1 repression inhibited cell proliferation and promoted apoptosis via miR-612/HOXA13 axis in CHF patients. According to the above results, our study revealed that LUCAT1 was decreased in CHF patients, which was correlated with poor prognosis of CHF patients. Furthermore, the downregulation of LUCAT1 inhibited cell proliferation and promoted cell apoptosis via targeting miR-612/HOXA13 axis. Our results elucidated a potential mechanism underlying cardiomyocyte apoptosis, which might be used as a promising prognostic marker and a potential target for CHF patients.

Background DICER1-AS1 is reported to promote the progression and disturb the cell cycle in osteosarcoma; however, its mechanism has rarely been studied. Materials and methods DICER1-AS1 expression levels were evaluated by qPCR and fluorescence in situ hybridization (FISH). The total, nuclear, and cytosolic levels of CDC5L were measured by western blotting and immunofluorescence (IF). Cell proliferation, apoptosis, and cell cycle analyses were conducted using the colony formation, CCK−8 assay, terminal transferase-mediated UTP nick end-labeling kit (TUNEL) assay, and flow cytometry. Levels of cell proliferation-, cell cycle-, and cell apoptosis-related proteins were determined by western blotting. RNA immunoprecipitation (RIP) and RNA pull-down assays were conducted to evaluate the relationship between DICER1-AS1 and CDC5L. Results LncRNA DICER1-AS1 was highly expressed in samples of osteosarcoma tissue and in osteosarcoma cell lines. DICER1-AS1 knockdown inhibited cell proliferation, promoted cell apoptosis, and disturbed the cell cycle. Moreover, DICER1-AS1 was found to bind with CDC5L, and knockdown of DICER-AS1 inhibited the nuclear transfer of CDC5L. DICER1-AS1 knockdown also reversed the effects of CDC5L overexpression on cell proliferation, apoptosis, and the cell cycle. Moreover, CDC5L inhibition suppressed cell proliferation, promoted cell apoptosis, and disturbed the cell cycle, and those effects were further enhanced by DICER1-AS1 knockdown. Finally, DICER1-AS knockdown inhibited tumor growth and proliferation, and promoted cell apoptosis in vivo. Conclusion LncRNA DICER1-AS1 knockdown inhibits the nuclear transfer of CDC5L protein, arrests the cell cycle, and induces apoptosis to suppress the development of osteosarcoma. Our results suggest a novel target (DICER1-AS1) for treatment of osteosarcoma.

Overexpression of microRNA-125b inhibits human acute myeloid leukemia cells invasion, proliferation and promotes cells apoptosis by targeting NF-κB signaling pathway

Molecular OncologyVolume 16, Issue 22 p. 4061-4061 Retraction NoticeOpen Access Retraction statement: Down-regulation of long noncoding RNA PVT1 inhibits esophageal carcinoma cell migration and invasion and promotes cell apoptosis via microRNA-145-mediated inhibition of FSCN1 This article retracts the following: Retracted: Down-regulation of long noncoding RNA PVT1 inhibits esophageal carcinoma cell migration and invasion and promotes cell apoptosis via microRNA-145-mediated inhibition of FSCN1 Si-Ning Shen, Ke Li, Ying Liu, Cheng-Liang Yang, Chun-Yu He, Hao-Rang Wang, Volume 13Issue 12Molecular Oncology pages: 2554-2573 First Published online: September 8, 2019 First published: 02 December 2022 https://doi.org/10.1002/1878-0261.13332AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat The above article, published online on 01 August 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Kevin Ryan, FEBS Press, and John Wiley and Sons Ltd. The retraction has been agreed due to observed anomalies in the Western blots on figure 3B and D, the flow cytometry plots in figure 2C, and the wound healing assays in figure 7A and C. The authors were unable to provide compelling raw data underpinning figures 2, 3, 7, and 8. Reference 1Shen S-N, Li K, Liu Y, Yang C-L, He C-Y, Wang H-R. Down-regulation of long noncoding RNA PVT1 inhibits esophageal carcinoma cell migration and invasion and promotes cell apoptosis via microRNA-145-mediated inhibition of FSCN1. Mol Oncol. 2019; 13: 2554– 73. https://doi.org/10.1002/1878-0261.12555 Volume16, Issue22Genomic and metabolic profiles of gliomasDecember 2022Pages 4061-4061 ReferencesRelatedInformation

Cytrarabine (Ara-c) promotes cell apoptosis by inhibiting the phosphorylation of Protein Kinase B (AKT/PKB)

Cisplatin-based chemotherapy resistance is a common issue for cancer clinical efficacy. Metformin is being studied for its possible anticancer effect. The present study aimed to investigate whether metformin affects the chemosensitivity of gastric cancer to cisplatin and reveal the molecular mechanism. In this study, the effects of combination therapy with metformin and cisplatin on cell viability, cell apoptosis, malondialdehyde, superoxide dismutase, reactive oxygen species level, glucose uptake, lactate production, protein level, and xenograft tumor formation were analyzed in gastric cancer cells. Immunohistochemical staining was performed to detect Ki67 expression in matched tumor samples. The results showed that NCI-N87 and SNU-16 cells were most resistant and sensitive to cisplatin, respectively. Metformin treatment increased the cisplatin sensitivity of gastric cancer by inhibiting cell viability and metabolic reprogramming and promoting cell apoptosis and oxidative stress. Furthermore, overexpression of nuclear factor erythroid 2-related factor 2 (Nrf2) reversed the effects of metformin in the cisplatin sensitivity of gastric cancer by inhibiting cell viability and metabolic reprogramming and promoting cell apoptosis and oxidative stress. Metformin activated p53 and AMPK pathways in cisplatin-induced NCI-N87 cells, which were reversed by upregulating Nrf2. BAY-3827 (AMPK inhibitor) or p-nitro-Pifithrin-α (p53 inhibitor) treatments also reversed the effects of metformin increased the cisplatin sensitivity of gastric cancer by inhibiting cell viability and metabolic reprogramming and promoting cell apoptosis and oxidative stress. These results suggest that metformin significantly increases chemosensitivity of gastric cancer to cisplatin by inhibiting Nrf2 expression and metabolic reprogramming and activating oxidative stress and the pathway of p53 and AMPK.

The purpose of this study was to investigate the potential role of Ileucyl-tRNA synthetase (IARS2) silencing in non-small cell lung cancer (NSCLC). The silencing of IARS2 in H1299 cells and A549 cells were performed by lentivirus encoding shRNAs. The efficiency of IARS2 silencing was detected by quantitative real time PCR and western blot. The effects of IARS2 silencing on cell growth, cell apoptosis, cell cycle and cell colony formation ability were assessed by cells counting, MTT assay, flow cytometer analysis and soft agar colony formation assay, respectively. Compared with negative control group, IARS2 was significantly knockdown by transfection with lentivirus encoding shRNA of IARS2. The IARS2 silencing significantly inhibited the cells proliferation and cells colony formation ability, induced cell cycle arrest at G1/S phase and promoted cell apoptosis. IARS2 silencing induced NSCLC cells growth inhibition, cell cycle arrest and promoted cell apoptosis. These results suggest that IARS2 may be anovel target for the treatment of NSCLC.

BackgroundThe phosphatase actin regulator-1 (PHACTR-1) gene on chromosome 6 encodes an actin and protein phosphatase 1 (PP1) binding protein, Phactr-1, which is highly expressed in brain tissues. Phactr-1 expression is involved in physiological and pathological cerebral microvascular events. This study aimed to investigate the role of expression of Phactr-1 in a mouse brain capillary endothelial cell line, bEnd.3, by knockdown the PHACTR-1 gene.Material/MethodsThree bEnd.3 cell groups were studied, CON (normal control cells), NC (control scramble transfected cells), and KD (cells with PHACTR-1 gene knockdown). The PHACTR-1 gene was knocked down using transfection with small hairpin RNA (shRNA). In the three cell groups cell proliferation, migration, and apoptosis were studied by MTT and colony formation assays, transwell and scratch assays, and flow cytometry. The related cell pathways of associated with Phactr-1 knockdown were studied by Western blot.ResultsPhactr-1 knockdown suppressed bEnd.3 cell proliferation and migration, promoted cell apoptosis, and downregulated the expressions of migration-associated proteins, including matrix metalloproteinase (MMP)-2 and MMP-9 and upregulated apoptosis-associated proteins, including Bax, Bcl-2, cleaved caspase-3, and caspase-3.ConclusionsPhactr-1 was shown to have a role in the inhibition of endothelial cell proliferation and migration, promoted cell apoptosis, and regulated matrix metalloproteinases and apoptosis-associated proteins. These findings indicate that the expression of the Phactr-1 should be studied further in the cerebral microvasculature, both in vitro and in vivo, regarding its potential as a diagnostic and therapeutic target for cerebral microvascular disease.

Lung cancer is the most common fatal type of cancer, demonstrating high incidence rates in both sexes. Therefore, it is of vital importance to devise more effective and targeted therapies to improve the treatment quality for patients. The present study aimed to determine the effects of microRNA (miR)-379-5p on cell proliferation and apoptosis, in addition to its underlying molecular mechanisms in lung cancer. Tumor and adjacent normal tissues were obtained from patients with NSCLC and transfection experiments in A549 cells were performed using miR-379-5p mimics and pcDNA3.1- β-arrestin-1 (ARRB1) overexpression plasmids. The cell proliferation rate was determined using a Cell Counting Kit-8 assay and the cell apoptotic rate was analyzed using flow cytometry. Additionally, the mRNA and protein expression levels of proliferation-related signaling (PI3K, p-PI3K, AKT and p-AKT) and apoptotic-related factors (Bcl-2, Bax and caspase-3) were detected using reverse transcription-quantitative PCR and western blotting, respectively. The results of the present study revealed that miR-379-5p expression levels were downregulated, whereas ARRB1 expression levels were significantly upregulated in NSCLC tissues and cell lines. Following the successful transfection of the miR-379-5p mimic and ARRB1 overexpression plasmid, it was revealed that the overexpression of miR-379-5p inhibited cell proliferation and promoted cell apoptosis, whereas ARRB1 overexpression reversed this inhibition over proliferation and promotion of apoptosis. The increased cell apoptotic rate observed in the miR-379-5p mimics group was associated with a significant downregulation and upregulation of Bcl-2, and Bax and caspase-3 expression levels, respectively. Finally, ARRB1 was identified as a target gene of miR-379-5p. In conclusion, the expression levels of miR-379-5p were demonstrated to be significantly downregulated in lung cancer. In addition, miR-379-5p overexpression led to the decreased expression levels of Bcl-2, phosphorylated (p)-PI3K/PI3K and p-AKT/AKT, and the increased expression levels of Bax and caspase-3. Overall, this resulted in the inhibition of cell proliferation and promoted cell apoptosis by directly targeting ARRB1. Therefore, miR-379-5p may be a potential target for NSCLC treatment due to its ability to inhibit cell proliferation and accelerate the apoptotic process.

Our previous study found that hydrogen gas (H2) could efficiently inhibit lung cancer progression; however, the underlying mechanisms still remains to be elucidated. The present study aimed to explore the roles of H2 in lung cancer cell autophagy, and reveal the effects of autophagy on H2-mediated lung cancer cell apoptosis and the underlying mechanisms. The expression levels of proteins associated with cell apoptosis and autophagy were detected using western blot analysis. Cell autophagy was inhibited by 3-methyladenine treatment or Beclin1 downregulation, while rapamycin was used to induce autophagy. Cell growth and apoptosis were detected using the Cell Counting Kit-8 and flow cytometry assays, respectively. The results demonstrated that cell apoptosis and autophagy were significantly enhanced in the A549 and H1975 lung cancer cell lines treated with H2. However, autophagy enhancement weakened H2 roles in promoting cell apoptosis and vice versa. In addition, it was found that H2 treatment induced marked decreases in the protein expression levels of phosphorylated STAT3 and Bcl2, and overexpression of STAT3 abolished H2 roles in promoting cell apoptosis and autophagy. Overall, the present study revealed that H2 can promote lung cancer cell apoptosis and autophagy via inhibiting the activation of STAT3/Bcl2 signaling and suppression of autophagy can enhance H2 roles in promoting lung cancer cell apoptosis.

miR-34c regulates the proliferation, apoptosis, and testosterone synthesis of bovine leydig cells by targeted ATG5 gene.

Background: This study aimed to investigate the regulatory role of long non-coding RNA associated with microvascular invasion in hepatocellular carcinoma ( lnc-MVIH ) in the progression of acute myeloid leukemia (AML) and the underlying mechanism. Methods: Lnc-MVIH expression was detected in AML cell lines AML-193, KG-1, HL-60, OCI-AML2 and primary normal bone marrow mononuclear cells (BMMC). The effect of lnc-MVIH knockdown on cell proliferation, apoptosis and miR-505 expression were detected by transfection of lnc-MVIH shRNA and control shRNA into KG-1 cells. And the effect of miR-505 knockdown on lnc-MVIH , cell proliferation, cell apoptosis as well as potential miR-505 target genes [ high mobility group box 1 ( HMGB1 ) and cyclin E2 ( CCNE2 )] in lnc-MVIH knockdown treated KG-1 cells was assessed by transfection of lnc-MVIH shRNA and lnc-MVIH shRNA & miR-505 shRNA into KG-1 cells. Results: Lnc-MVIH expression was elevated in AML-193, KG-1, OCI-AML2 cell lines, but similar in HL-60 cell line compared with primary normal BMMC. Lnc-MVIH knockdown inhibited cell proliferation but promoted cell apoptosis in KG-1 cells, meanwhile miR-505 expression was increased by lnc-MVIH knockdown in KG-1 cells. And in rescue experiments, miR-505 knockdown had no effect on expression of lnc-MVIH , while it increased the expressions of HMGB1 and CCNE2 , promoted cell proliferation, inhibited cell apoptosis in lnc-MVIH knockdown treated KG-1 cells. Conclusions: Lnc-MVIH knockdown inhibits cell proliferation but promotes cell apoptosis via regulating miR-505 mediated HMGB1 and CCNE2 in AML.

Human cytomegalovirus (HCMV) can cause congenital diseases and opportunistic infections in immunocompromised individuals. Its functional proteins and microRNAs (miRNAs) facilitate efficient viral propagation by altering host cell behaviour. Identification of functional target genes of miRNAs is an important step in studies on HCMV pathogenesis. In this study, Glutaminyl-tRNA Synthetase (QARS), which could regulate signal transduction pathways for cellular apoptosis, was identified as a direct target of hcmv-miR-US4-1. Apoptosis assay revealed that as silence of QARS by ectopic expression of hcmv-miR-US4-1 and specific small interference RNA of QARS can promote cell apoptosis in HCMV-infected HELF cells. Moreover, viral growth curve assays showed that hcmv-miR-US4-1 benefits the discharge of infectious virus particles. However, silence of hcmv-miR-US4-1 by its specific inhibitor overturned these effects. These results imply that hcmv-miR-US4-1 might have the same effects during HCMV nature infection. In general, hcmv-miR-US4-1 may involve in promoting cell apoptosis and benefiting discharge of infectious virus particles via down-regulation of QARS in HCMV-infected HELF cells.