Retracted Article: Long noncoding RNA ANRIL protects cardiomyocytes against hypoxia/reoxygenation injury by sponging miR-195-5p and upregulating Bcl-2

Long noncoding RNAs have been widely accepted to play important roles in acute myocardial infarction (AMI). The dysregulation of cyclin-dependent kinase inhibitor 2B antisense RNA 1 (ANRIL) was discovered in AMI patients. Nevertheless, the detailed role and molecular mechanisms of ANRIL in AMI remain indistinct. The levels of ANRIL, miR-195-5p and Bcl-2 mRNA were determined by qRT-PCR. western blot was performed to assess the expression of Bcl-2, Bax, Cyclin D1 and p21. Cell proliferation was detected by CCK-8 assay, and cell apoptosis was measured by flow cytometry. The targeted correlation between ANRIL and miR-195-5p was confirmed by the dual-luciferase reporter and RNA pull-down assays. Our data revealed that ANRIL was downregulated and miR-195-5p was upregulated in the serum of AMI patients and hypoxia/reoxygenation (H/R)-induced myocardial cells. ANRIL upregulation or miR-195-5p knockdown alleviated H/R-induced myocardial cell injury. Moreover, ANRIL sequestered miR-195-5p by acting as a sponge of miR-195-5p. ANRIL upregulated Bcl-2 expression by sponging miR-195-5p. Additionally, ANRIL overexpression alleviated H/R-induced myocardial cell injury by upregulating Bcl-2. In conclusion, our study indicated that ANRIL upregulation alleviated H/R-induced myocardial cell injury partially through sponging miR-195-5p and upregulating Bcl-2, highlighting its role as a promising mediator for new therapies for AMI treatment.

Long noncoding RNAs have been widely accepted to play important roles in acute myocardial infarction (AMI).     

Retracted Article: Long noncoding RNA PCA3 regulates glycolysis,viability and apoptosis by mediating the miR-1/CDK4 axis in prostate cancer

Prostate cancer is one of the common tumor malignancies in men worldwide. Although long noncoding RNAs (lncRNAs) have been demonstrated to play essential roles in the progression of prostate cancer, the roles and potential mechanism of lncRNA prostate cancer antigen 3 (PCA3) remain poorly understood. In the present study, we investigated the role of PCA3 in aerobic glycolysis, viability and apoptosis in prostate cancer cells and probed the interaction between PCA3 and microRNA-1 (miR-1)/cyclin-dependent kinase 4 (CDK4). Here we found that PCA3 and CDK4 were up-regulated while miR-1 was down-regulated in prostate cancer tissues and cells. Moreover, knockdown of PCA3 inhibited aerobic glycolysis and viability and induced apoptosis in prostate cancer cells. Intriguingly, PCA3 was bound to miR-1 and inhibition of miR-1 reversed the regulatory effect of PCA3 knockdown on aerobic glycolysis, viability and apoptosis in prostate cancer cells. Besides, CDK4 was indicated as a target of miR-1 and it was regulated by PCA3 through functioning as a competing endogenous RNA (ceRNA) of miR-1 in prostate cancer cells. The results indicated that PCA3 might drive aerobic glycolysis, viability and apoptosis by regulating the miR-1/CDK4 axis in prostate cancer cells, providing a promising avenue for treatment of prostate cancer.

We proved that PCA3 regulated aerobic glycolysis, viability and apoptosis by regulating the miR-1/CDK4 axis in prostate cancer cells.     

Retracted Article: Long non-coding RNA KCNQ1OT1 regulates cell proliferation,apoptosis and chemo-sensitivity through modulating the miR-186-5p/NCAM1 axis in acute myeloid leukemia cells

Recent studies show that lncRNA KCNQ1OT1 and microRNA-186-5p (miR-186-5p) are involved in various human cancers. Moreover, it is reported that KCNQ1OT1 expression is upregulated in acute myeloid leukemia (AML). However, their roles in AML remain unknown. This study aimed to reveal the functional mechanism of KCNQ1OT1 and miR-186-5p in AML development. Quantitative real time polymerase chain reaction (qRT-PCR) was performed to detect the levels of genes. Cell proliferation and apoptosis were assessed by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry analysis respectively. A western blot assay was carried out to examine the protein levels. In addition, the interaction between miR-186-5p and KCNQ1OT1 or neural cell adhesion molecule 1 (NCAM1) was predicted by bioinformatics analysis tool starbase2.0 and confirmed by the dual luciferase reporter assay. KCNQ1OT1 and NCAM1 expressions were increased and miR-186-5p expression was decreased in AML samples and cells. The depletion of KCNQ1OT1 inhibited cell proliferation, and promoted apoptosis and chemo-sensitivity in AML. In addition, the upregulation of miR-186-5p suppressed AML cell proliferation, and induced apoptosis and chemo-sensitivity. Interestingly, KCNQ1OT1 directly downregulated miR-186-5p expression and miR-186-5p decreased NCAM1 expression by binding to the 3′ untranslated region (UTR) of NCAM1 mRNA. Furthermore, miR-186-5p knockdown or NCAM1 overexpression reversed the effects of KCNQ1OT1 depletion on AML cell progression. Our results firstly revealed a linear relationship between KCNQ1OT1, miR-186-5p, and NCAM1, and demonstrated that KCNQ1OT1 mediated AML cell progression via regulating the miR-186-5p/NCAM1 axis, revealing functional mechanisms of KCNQ1OT1 and miR-186-5p in AML development.

Recent studies show that lncRNA KCNQ1OT1 and microRNA-186-5p (miR-186-5p) are involved in various human cancers.     

Retracted Article: Knockdown of NEAT1 ameliorated MPP+-induced neuronal damage by sponging miR-221 in SH-SY5Y cells

Long noncoding RNAs (lncRNAs) have recently attracted increasing attention for their involvement in a wide variety of human neurodegenerative diseases, including Parkinson''s disease (PD). The purpose of the present study was to investigate the functional role and underlying mechanism of NEAT1 in PD. qRT-PCR was used to assess the expression of NEAT1 and miR-221, and the expression levels of Bcl-2 and Bax were detected by western blot. Cell viability and apoptosis were determined by CCK-8 assay and flow cytometry, respectively. The changes of oxidative stress and neuroinflammation were evaluated by ELISA assay and qRT-PCR, respectively. The targeted interaction between NEAT1 and miR-221 was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Our data supported that MPP⁺ treatment elevated NEAT1 expression in dose- and time-dependent manners in SH-SY5Y cells, and NEAT1 silencing relieved MPP⁺-induced suppression of cell viability and enhancement of cell apoptosis in SH-SY5Y cells. Moreover, NEAT1 silencing alleviated MPP⁺-induced promotion of oxidative stress and neuroinflammation in SH-SY5Y cells. NEAT1 directly targeted miR-221 and negatively regulated miR-221 expression. More importantly, miR-221 mediated the protective effect of NEAT1 knockdown, as evidenced by the restoration of cell viability, cell apoptosis, oxidative stress and neuroinflammation in MPP⁺-induced SH-SY5Y cells. In conclusion, our study suggested that NEAT1 silencing alleviated MPP⁺-induced neuronal damage by sponging miR-221 in SH-SY5Y cells, highlighting the role of NEAT1 as a potential molecular target for PD therapy.

Long noncoding RNAs (lncRNAs) have recently attracted increasing attention for their involvement in a wide variety of human neurodegenerative diseases, including Parkinson''s disease (PD).     

Retracted Article: Long noncoding RNA ANRIL knockdown increases sensitivity of non-small cell lung cancer to cisplatin by regulating the miR-656-3p/SOX4 axis

Long noncoding RNAs (lncRNAs) are implicated in the development of chemoresistance in many cancers. However, the effect and mechanism of lncRNA antisense noncoding RNA in the INK4 locus (ANRIL) on cisplatin (CDDP) resistance in non-small cell lung cancer (NSCLC) remain unclear. The levels of ANRIL, microRNA (miR)-656-3p and sex-determining region Y-related high-mobility group box 4 (SOX4) in NSCLC tissues and cells were detected by quantitative real-time polymerase chain reaction or western blotting. Cell viability, apoptosis, migration and epithelial-to-mesenchymal transition (EMT) were assessed by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT assay), flow cytometry, trans-well assays and western blotting, respectively. The xenograft model was established using CDDP-resistant NSCLC cells. The target association between miR-656-3p and ANRIL or SOX4 was validated by luciferase reporter assay and RNA immunoprecipitation. ANRIL expression was increased in CDDP-resistant NSCLC tissues and cells. Knockdown of ANRIL decreased cell viability, migration and EMT but induced apoptosis in CDDP-resistant NSCLC cells. Moreover, silencing of ANRIL reduced xenograft tumor growth in vivo. miR-656-3p was targeted by ANRIL and its exhaustion attenuated the suppressive role of ANRIL knockdown in CDDP resistance in NSCLC cells. SOX4 acted as a target of miR-656-3p and was positively regulated by ANRIL. Collectively, interference of ANRIL repressed CDDP resistance through promoting apoptosis and inhibiting cell viability, migration and EMT by up-regulating miR-656-3p and down-regulating SOX4, indicating a new target to improve the chemotherapeutic efficacy in NSCLC.

Long noncoding RNAs (lncRNAs) are implicated in the development of chemoresistance in many cancers.     

Retracted Article: Long noncoding RNA DLEU1 promotes cell proliferation and migration of Wilms tumor through the miR-300/HOXC8 axis

Wilms tumor (nephroblastoma) is the most common primary renal tumor occurring in children. Long noncoding RNA (lncRNA) deleted in lymphocytic leukemia 1 (DLEU1) is an identified cancer-associated lncRNA that plays an important role in various cancers. However, the role of DLEU1 in Wilms tumor remains unclear. In the present study, we examined the expression and role of DLEU1 in Wilms tumor. We demonstrated that DLEU1 expression was upregulated in Wilms tumor tissues and cell lines. Knockdown of DLEU1 significantly inhibited the proliferation, migration and invasion of GHINK-1 cells. Furthermore, DLEU1 directly sponged miR-300 and regulated the expression level of miR-300 in GHINK-1 cells. Inhibition of miR-300 reversed the inhibitory effects of DLEU1 downregulation on cell proliferation, migration and invasion. Homeobox C8 (HOXC8) was found to be a target gene of miR-300 and mediated the role of miR-300 in GHINK-1 cells. In conclusion, these findings indicated that DLEU1 executed an oncogenic role in Wilms tumor via regulating the miR-300/HOXC8 axis, indicating that DLEU1 might be a therapeutic target for the treatment of Wilms tumor.

Wilms tumor (nephroblastoma) is the most common primary renal tumor occurring in children.     

LncRNA PTPRG-AS1通过靶向miR-5590-3p调控乳腺癌细胞增殖、迁移和侵袭的研究

目的 探讨LncRNA PTPRG-AS1对乳腺癌细胞增殖、迁移和侵袭的影响及可能机制.方法 以正常乳腺上皮细胞MCF-10A为对照,qRT-PCR法检测乳腺癌细胞系(MCF-7、T47D和BT549)中LncRNA PTPRG-AS1和miR-5590-3p表达.分别转染si-LncRNA PTPRG-AS1、miR...     

Long non coding RNA UCA1 contributes to the autophagy and survival of colorectal cancer cells via sponging miR-185-5p to up-regulate the WISP2/β-catenin pathway

The estimated number of new cases of colorectal cancer (CRC) will increase to 140 250 in 2018 worldwide. The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has recently been shown to be dysregulated in CRC, which plays an important role in the progression of CRC. However, the biological role and the underling mechanism of UCA1 in the carcinogenesis of CRC remain unclear. Herein, we found that UCA1 was aberrantly upregulated in two CRC cell lines (SW620 and HT29) compared to colorectal cell CCD-18Co. UCA1 knockdown inhibited the apoptosis, growth and autophagy of CRC cell lines in vitro. Furthermore, UCA1 could act as an endogenous sponge by directly interacting with miR-185-5p and downregulation miR-185-5p expression. In addition, UCA1 could reverse the inhibitory effect of miR-185-5p on the growth and autophagy of CRC cells, which might be involved in the derepression of member 1 (WNT1)-inducible signaling pathway protein 2 (WISP2, a target gene of miR-185-5p) expression and the activation of the WISP2/β-catenin signaling pathway. In vivo, the present study elucidates a novel UCA1-miR-185-5p-WISP2-Wnt/β-catenin axis in CRC, which may help us to understand the pathogenesis and the feasibility of lncRNA-directed diagnosis and therapy of CRC.

The estimated number of new cases of colorectal cancer (CRC) will increase to 140 250 in 2018 worldwide.     

Retracted Article: Long non-coding RNA MEG3 inhibits cell proliferation,migration, invasion and enhances apoptosis in non-small cell lung cancer cells by regulating the miR-31-5p/TIMP3 axis

Non-small cell lung cancer (NSCLC) is a malignant lung cancer and accounts for 80% of lung cancer-related deaths. Long non-coding RNA maternally expressed gene 3 (MEG3) has been identified as a tumor suppressor in multiple cancers. However, the regulatory mechanism of MEG3 in NSCLC development is still largely unknown. The expression levels of MEG3, microRNA-31-5p (miR-31-5p) and tissue inhibitor of metalloproteinase 3 (TIMP3) in NSCLC tumors and cells were measured by quantitative real time polymerase chain reaction (qRT-PCR). Cell viability, apoptosis, migration and invasion were detected by cell counting kit-8 (CCK-8), flow cytometry, western blotting and transwell assays, respectively. Xenograft mouse models were established by subcutaneously injecting NSCLC cells stably transfected with Lenti-pcDNA or Lenti-MEG3. The interaction between miR-31-5p and MEG3 or TIMP3 was validated by luciferase reporter and RNA immunoprecipitation (RIP) assays. MEG3 and TIMP3 levels were up-regulated, whereas miR-31-5p expression was down-regulated in NSCLC tumors and cells compared with normal tissues and cells. Overexpression of MEG3 repressed cell proliferation, migration and invasion, but induced apoptosis in NSCLC cells. More importantly, MEG3 effectively hindered tumor growth in vivo. Next, luciferase reporter and RIP assays confirmed the interaction between miR-31-5p and MEG3 or TIMP3. Pearson''s correlation coefficient revealed that miR-31-5p was inversely correlated with MEG3 or TIMP3. Rescue experiments indicated that MEG3 regulated TIMP3 expression by sponging miR-31-5p in NSCLC cells. Thus, MEG3 inhibited cell proliferation, migration and invasion, but enhanced apoptosis in NSCLC cells through up-regulating TIMP3 expression by regulating miR-31-5p, indicating novel biomarkers for the therapy of NSCLC.

Non-small cell lung cancer (NSCLC) is a malignant lung cancer and accounts for 80% of lung cancer-related deaths.     

Retracted Article: Overexpression of circ_0034642 contributes to hypoxia-induced glycolysis,cell proliferation,migration and invasion in gliomas by facilitating TAGLN2 expression via sponging miR-625-5p

Glioma is an aggressive brain cancer with poor prognosis and high invasiveness. Dysregulation of circular RNAs (circRNAs) has been widely discovered in various cancers, including glioma. However, the molecular mechanism of circ_0034642 in glioma is still unclear. The expression of circ_0034642, microRNA (miR)-625-5p and transgelin-2 (TAGLN2) in glioma tumors and cells was detected by performing a quantitative real-time polymerase chain reaction (qRT-PCR). The stability of circ_0034642 was determined by carrying out RNase R treatment. Cell proliferation was evaluated by performing the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Glycolysis was analyzed by measuring the extracellular acidification rate (ECAR) using glucose detection and lactic acid detection kits. Cell migration and invasion were determined by performing the transwell assay. Protein expression levels of the proteins hexokinase 2 (HK2), matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-9 (MMP9) and TAGLN2 were analyzed using western blots. The interaction between miR-625-5p and circ_0034642 or TAGLN2 was proved using a dual-luciferase reporter system. Animal models were established by subcutaneously injecting glioma cells stably transfected with sh-NC or sh-circ_0034642. Circ_0034642 and TAGLN2 were overexpressed whereas miR-625-5p was expressed at low levels in glioma tumors and cells. Moreover, circ_0034642 and TAGLN2 were upregulated while miR-625-5p was downregulated under hypoxic conditions in a time-dependent manner. Next, elimination of circ_0034642 was shown to inhibit cell glycolysis, proliferation, migration and invasion under hypoxic conditions in gliomas. Then, we found that circ_0034642 acted as a “sponge” of miR-625-5p while TAGLN2 acted as a target of miR-625-5p. In addition, recovery of circ_0034642 attenuated the repression mediated by miR-625-5p on glioma cell glycolysis and progression under hypoxic conditions. Meanwhile, an inhibitor of miR-625-5p alleviated TAGLN2 deficiency-induced inhibition of glioma cell development under hypoxic conditions. We also discovered that circ_0034642 could interact with miR-625-5p and further alter the expression of TAGLN2. Lastly, a circ_0034642 knockdown hindered tumor growth in vivo by regulating the miR-625-5p/TAGLN2 axis. Enhanced expression of circ_0034642 was found to promote cell glycolysis, proliferation, migration and invasion under hypoxic conditions in gliomas by sponging miR-625-5p to improve TAGLN2 expression, providing prospective biomarkers for the diagnosis of glioma.

Circ_0034642 was upregulated under hypoxic conditions in gliomas.     

Retracted Article: MiR-182-5p and miR-96-5p increased hepatocellular carcinoma cell mobility,proliferation and cisplatin resistance partially by targeting RND3

We investigated whether miR-182-5p or miR-96-5p could increase hepatocellular carcinoma (HCC) development by targeting Rho Family GTPase 3 (RND3) gene expression. The expression levels of miR-182-5p, miR-96-5p and mRNA/protein of RND3 in non-HCC liver tissue, HCC tissue and adjacent tissue specimens were evaluated by RT-qPCR and western blot. Patient-derived HCC cell culture was established, and miR-182-5p or miR-96-5p agomir or antagomir treatment was performed to mimic the overexpression or knockdown of the two miRNAs. HCC cell mobility in vitro was monitored by trans-well migration and invasion assay, while HCC cell growth in vitro was evaluated by cell viability, proliferation and apoptosis assay. HCC cell apoptosis was further investigated by caspase-3/-8/-9 activity assay. MiR-182-5p and miR-96-5p were significantly upregulated in HCC tissue specimens compared with non-HCC or adjacent tissue specimens, inversely correlating to RND3 mRNA expression level. Treatment with miR-182-5p or miR-96-5p agomir significantly reduced RND3 mRNA/protein expression level in HCC cells. MiR-182-5p- or miR-96-5p-targeting RND3 mRNA was verified by luciferase reporter assay and AGO2-RNA immunoprecipitation assay. MiR-182-5p or miR-96-5p agomir treatment significantly rescued HCC cell migration and invasion in vitro that were repressed by RND3 overexpression, during which ROCK1 and ROCK2 inhibition were involved. MiR-182-5p or miR-96-5p agomir treatment also increased HCC cell proliferation and cisplatin resistance in vitro, which could be antagonized by RND3 overexpression or ROCK inhibition. Thus, miR-182-5p and miR-96-5p increased HCC cell mobility, proliferation and cisplatin resistance in vitro partially by targeting RND3.

We investigated whether miR-182-5p or miR-96-5p could increase hepatocellular carcinoma (HCC) development by targeting Rho Family GTPase 3 (RND3) gene expression.     

Retracted Article: Circular RNA PTK2 modifies the progression and radiosensitivity in gastric cancer via miR-369-3p/ZEB1 axis

Gastric cancer (GC) is one of the common cancers worldwide. Emerging findings imply that aberrant expression of circular RNA_0003221 (circPTK2) is involved in GC. Nevertheless, the function of circPTK2 in GC needs more explanation. Profiles of circPTK2, microRNA (miR)-369-3p, and zinc finger E-box binding homeobox 1 (ZEB1) were determined by quantitative real-time polymerase chain reaction assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and transwell assays were employed to estimate cell proliferation, apoptosis, and mobility in GC cells, respectively. Meanwhile, levels of ZEB1 and other indicated proteins were tested using western blot. Survival fraction was assessed utilizing clonogenic assay. Additionally, the role of circPTK2 in tumorigenesis was investigated via a xenograft tumor model. Dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays were conducted to confirm the interrelation between miR-369-3p and circPTK2 or ZEB1. Levels of circPTK2 and ZEB1 were markedly augmented, but miR-369-3p was downregulated in GC tissues and cells. CircPTK2 depletion restrained cell growth, metastasis, and epithelial–mesenchymal transition, and promoted radiosensitivity in GC cells. And circPTK2 depletion reduced tumor growth and metastasis in vivo. Moreover, the effect of circPTK2 silencing on cellular phenotypes and radiosensitivity was regained by miR-369-3p inhibitor. Furthermore, upregulation of ZEB1 could overturn miR-369-3p mimic-induced effect on cell metastasis and radiosensitivity of GC cells. Mechanically, circPTK2 was a sponge of miR-369-3p to separate ZEB1. CircPTK2/miR-369-3p/ZEB1 axis modulated cell behaviors and radiosensitivity in GC; thus circPTK2 might serve as a promising target for GC therapy.

Circular RNA PTK2 regulates the cell proliferation, apoptosis, mobility and radiosensitivity via ZEB1 by sponging miR-369-3p in gastric cancer.     

Retracted Article: PVT1 depletion protects cartilage ATDC5 cells against LPS-induced inflammatory injury by regulating the miR-24/ADAMTS5 axis

Background: Osteoarthritis is a common chronic arthritis among adults and cartilage dysfunction is largely responsible for osteoarthritis development. Long noncoding RNAs (lncRNAs) have been reported to be related to osteoarthritis progression. However, the mechanism that underlies the effect of lncRNA plasmacytoma variant translocation 1 (PVT1) on inflammatory injury in cartilage ATDC5 cells remains elusive. Methods: The quantity of PVT1 and microRNA-24 (miR-24) was detected in human cartilage ATDC5 cells after transfection of si-PVT1, si-con, PVT1 or pcDNA and lipopolysaccharide (LPS) treatment for 12 h. Inflammatory injury was investigated using cell viability, apoptosis and secretion of inflammatory cytokines. The interaction of miR-24 with PVT1 or a disintegrin-like metalloproteinase with thrombospondin motifs 5 (ADAMTS5) was probed by bioinformatics, luciferase activity, RNA pull down and Ago1 RNA immunoprecipitation (RIP) assays. The effect of PVT1 and miR-24 on ADAMTS5 expression was evaluated in ATDC5 cells by western blotting (WB). Results: Treatment of LPS induced elevated PVT1 and reduced miR-24 expression in ATDC5 cells. Moreover, LPS inhibited cell viability, increased apoptosis and inflammatory cytokine production. However, PVT1 depletion attenuated LPS-induced inflammatory injury in ATDC5 cells. In addition, miR-24 directly bound to PVT1 and its deficiency reversed the effect of PVT1 deletion in LPS-treated ATDC5 cells. Furthermore, ADAMTS5 was a target of miR-24 and aberrant expression of ADAMTS5 was regulated by PVT1 and miR-24. Conclusion: PVT1 abrogation protected against LPS-induced inflammatory injury in ATDC5 cells by coordinating with the miR-24/ADAMTS5 axis, opening up a novel avenue for osteoarthritis therapeutics.

Osteoarthritis is a common chronic arthritis among adults and cartilage dysfunction is largely responsible for osteoarthritis development.     

Retracted Article: Knockdown of TUG1 aggravates hypoxia-induced myocardial cell injury via regulation of miR-144-3p/Notch1

Myocardial infarction is a common cause of mortality in cardiovascular diseases. Long noncoding RNA taurine-upregulated gene 1 (TUG1) has been reported to play an important role in the regulation of myocardial injury; however, the mechanism via which TUG1 participates in myocardial infarction is unknown. In this study, hypoxia-treated cardiomyoblast H9c2 cells were used as a model of myocardial infarction. Cell transfection was conducted using Lipofectamine 2000 for 48 h. Hypoxia-induced injury was investigated by cell viability and apoptosis using the trypan blue exclusion method, flow cytometry and Western blot. The expressions of TUG1, microRNA-144-3p (miR-144-3p) and the Notch1 pathway were investigated by a quantitative real-time polymerase chain reaction and Western blot. The association between miR-144-3p and TUG1 or Notch1 was analyzed by bioinformatics analysis and luciferase reporter assay. Our results showed that hypoxia-induced H9c2 cell injury led to the inhibition of cell viability and promotion of apoptosis. Moreover, hypoxia could cause the up-regulation of TUG1 and Notch1 expression and down-regulation of miR-144-3p. The knockdown of TUG1 or overexpression of miR-144-3p aggravated the hypoxia-induced viability suppression and apoptosis production in the H9c2 cells. Moreover, miR-144-3p was indicated to be bound to TUG1, and its abrogation reversed the silencing of TUG1-mediated promotion of hypoxia-induced injury. In addition, Notch1 was a target of miR-144-3p, and its restoration attenuated the miR-144-3p-mediated promotion of hypoxia-induced injury. Moreover, TUG1 interference alleviated the hypoxia-induced activation of the Notch1/Hes-1 pathway via the regulation of miR-144-3p. In conclusion, the interference of TUG1 contributed to hypoxia-induced injury via the regulation of the miR-144-3p/Notch1/Hes-1 pathway; this indicated a novel mechanism for understanding the pathogenesis of myocardial infarction.

Myocardial infarction is a common cause of mortality in cardiovascular diseases.     

Retracted Article: LncRNA ZEB2-AS1 regulates the drug resistance of acute myeloid leukemia via the miR-142-3p/INPP4B axis

Dysregulation of long noncoding RNAs (lncRNAs) has been reported to participate in the process of chemoresistance in multiple cancers, including acute myeloid leukemia (AML). LncRNA zinc finger E-box binding homeobox 2 antisense RNA 1 (ZEB2-AS1) has been reported to be up-regulated in AML. However, the biological role of ZEB2-AS1 remains to be determined. Quantitative real time polymerase chain reaction (qRT-PCR) was used to detect the levels of ZEB2-AS1, miR-142-3p and inositol polyphosphate-4-phosphatase type II B (INPP4B). The cell viability and apoptosis were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. Western blotting was applied to analyze levels of BCL2 apoptosis regulator (Bcl-2), BCL2 associated X, apoptosis regulator (Bax), cleaved-caspase-3 and INPP4B. The interaction among ZEB2-AS1, miR-142-3p and INPP4B was verified by dual-luciferase reporter assay and RNA pull-down assay. The levels of ZEB2-AS1 and INPP4B were significantly elevated in AML and chemo-resistance tissues, as well as in THP-1 and THP-1/ADR cells. ZEB2-AS1 elevated the IC50 of ADR, and suppressed cell apoptosis of AML cells, while ZEB2-AS1 increased Bcl-2 expression and decreased the levels of Bax and cleaved-caspase-3. ZEB2-AS1 could enhance the resistance in THP-1 and THP-1/ADR cells. ZEB2-AS1 could sponge miR-142-3p, and ZEB2-AS1 reduced the promotion effect of miR-124-3p on the sensitivity of AML cells. Furthermore, IPNN4B was revealed as a target gene of miR-142-3p. More interestingly, suppression of IPNN4B by shRNA reversed the inhibitory effect of ZEB2-AS1 on the sensitivity of AML cells. LncRNA ZEB2-AS1 promoted ADR resistance of AML via regulating INP4B expression by sponging miR-142-3p, providing a novel therapeutic target for drug resistance of AML.

Dysregulation of long noncoding RNAs (lncRNAs) has been reported to participate in the process of chemoresistance in multiple cancers, including acute myeloid leukemia (AML).     

Retracted Article: Aclarubicin regulates glioma cell growth and DNA damage through the SIRT1/PI3K/AKT signaling pathway

Aclarubicin (ACR), an anthracycline anti-tumor agent, is known to play important roles in cancer. Evidence has suggested that ACR has therapeutic effects on rats intracranially implanted with C6 glioma cells. However, the function and mechanism of ACR in glioma cells remain elusive. In this study, we examined the effects of ACR on glioma cell growth, apoptosis, and DNA damage. Our results showed that treatment with different concentrations of ACR (1, 2, and 5 μM) markedly impeded glioma cell survival, significantly decreased cell proliferation, and increased cell apoptosis and caspase-3 activity. Furthermore, ACR treatment promoted DNA damage through phosphorylation of ATM and CHK1 in U87 and U251 cells. Treatment with ACR also increased sirtuin 1 (SIRT1) expression and inhibited phosphatidylinositol 3′-kinase (PI3K)/AKT pathway activation. Interestingly, we found that AKT overexpression reversed the effects of ACR on glioma cell survival, proliferation, apoptosis, and DNA damage. Thus, our data suggest that ACR induces apoptosis and DNA damage in U87 and U251 cells through the SIRT1/PI3K/AKT signaling pathway.

Aclarubicin (ACR), an anthracycline anti-tumor agent, is known to play important roles in cancer.