lncRNA TP73-AS1 Research Articles

Statement of Retraction: Down-regulated lncRNA TP73-AS1 reduces radioresistance in hepatocellular carcinoma via the PTEN/Akt signaling pathway

Statement of Retraction: Down-regulated lncRNA TP73-AS1 reduces radioresistance in hepatocellular carcinoma via the PTEN/Akt signaling pathway

LncRNA TP73-AS1 enhances the malignant properties of colorectal cancer by increasing SPP-1 expression through miRNA-539-5p sponging.

Colorectal cancer (CC) is one of the most aggressive cancers, with a high mortality rate worldwide. This study focuses on the mechanism of CC to explore the effective therapeutic targets. We determined that LncRNA TP73-AS1 (TP-73-AS1) expression was significantly increased in CC tissues. TP73-AS1 silencing dynamically inhibited the proliferation, migratory and invasive capacity in CC cells. Mechanistically, we found that TP73-AS1 targeted miR-539-5p and miR-539-5p silencing could promote the migratory and invasive capacity in CC cells. Further study also confirmed that SPP-1 expression significantly increased after co-transfection of miR-539-5p inhibitors. Knockdown the SPP-1 can reverse malignant properties of CC cells. Si-TP73-AS1 suppressed the tumor growth of CC cells in vivo. In a word, we found that TP73-AS1 enhances the malignant properties of colorectal cancer by increasing SPP-1 expression through miRNA-539-5p sponging. And our study provides a potential therapeutic target of CC.

LncRNA TP73-AS1 Exacerbates the Non-Small-Cell Lung Cancer (NSCLC) Process via Regulating miR-125a-3p-Mediated ACTN4.

Background LncRNA TP73-AS1 has been revealed to exert a noteworthy impact on the occurrence and advancement of different cancers. In this study, we explored the function of TP73-AS1 in tumor growth, cell progression as well as the relevant molecular mechanism in non-small-cell lung cancer (NSCLC). Methods QRT-PCR was employed to assess the expression of TP73-AS1, miR‐125a-3p, and actinin alpha 4 (ACTN4) in NSCLC cells. The biological effect of TP73-AS1 on NSCLC cells was assessed by cell transfection, CCK8, and transwell experiments. We further predicted the interaction among RNAs (TP73-AS1, miR-125a-3p, and ACTN4) through bioinformatics online tools and verified via luciferase reporter, RNA immunoprecipitation, and qRT-PCR assays. Xenograft models of SPC-A1 cells were conducted to test how TP73-AS1 regulates tumorigenesis. Western blot, as well as the immunohistochemistry (IHC) assays, was utilized to measure the expression levels. Functions of TP73-AS1 in NSCLC progression through the miR-125a-3p/ACTN4 axis were investigated by rescue experiments. Results Knockdown of TP73-AS1 suppressed the growth and simultaneously attenuated the migration and invasion ability of NSCLC SPC-A1 and A549 cells. Bioinformatics and molecular mechanism assays demonstrated that TP73-AS1 could bind to miR-125a-3p/ACTN4 and regulate their expression. Moreover, the rescued‐function experiment demonstrated that suppressing miR-125a-3p or elevating ACTN4 turned around the suppression effect of sh-TP73-AS1 on NSCLC progression. TP73-AS1 inhibition could also inhibit the NSCLC tumor growth and correspondingly regulated the expression of miR-125a-3p and ACTN4 in the tumor xenograft model. Conclusion The present study indicated that TP73-AS1 affects NSCLC progression through a new competitive RNA (ceRNA) regulatory network of miR-125a-3p/ACTN4, providing an underlying target for NSCLC treatment in the future.

TP73-AS1 as a predictor of clinicopathological parameters and prognosis in human malignancies: a meta and bioinformatics analysis

BackgroundLong non-coding RNA P73 antisense RNA 1 T (non-protein coding), also known as Lnc RNA TP73-AS1, is dysregulated in various tumors but the correlation between its expression and clinicopathological parameters and/or prognoses in cancer patients is inconclusive. Here, we performed a meta-analysis to evaluate the prognostic value of Lnc RNA TP73-AS1 for malignancies.MethodsWe systematically searched four online databases including PubMed, the Web of Science, Embase, and the Cochrane Library for eligible articles published up to June 29/2020. Odds ratios (ORs) and Pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the association of TP73-AS1 expression with prognostic and clinicopathological parameters. We further validated TP73-AS1 expression in various malignancies and its potential prognostic value using the GEPIA online database. We predicted potential biological processes and relevant signal mechanisms through the public databases.ResultsA total of 26 studies examining 14 cancers were analyzed to evaluate the relationship between TP73-AS1 expression, clinicopathological features and prognostic indicators. The results indicated that TP73-AS1 expression markedly correlates with TNM stage (OR = 3.27,95% CI:2.43–4.39, P < 0.00001), tumor size (OR = 3.00, 95%CI:2.08–4.35, P < 0.00001), lymph node metastasis (OR = 2.77, 95%CI:1.42–5.38,P < 0.00001) and distant metastasis (OR = 4.50,95%CI:2.62–7.73,P < 0.00001). No correlation with age (OR = 1.12,95%CI:0.77–1.64, P > 0.05), gender (OR = 1.08, 95%CI:0.84–1.38, P > 0.05) or differentiation (OR = 1.39, 95%CI:0.71–2.70, P = 0.340) was observed. TP73-AS1 overexpression was a biomarker of poor Overall survival(OS)(HR = 1.85,95%CI:1.53–2.22, P < 0.00001) and Disease-Free-Survival (DFS) (HR = 1.57,95%CI:1.03–2.42, P < 0.05). Dysregulated TP73-AS1 expression and its prognostic value in various cancers was validated based on The Cancer Genome Atlas (TCGA). Further biological function predictions indicated that TP73-AS1 was involved in pro-oncogenic signaling.ConclusionsThe upregulation of Lnc RNA TP73-AS1 was related to detrimental clinicopathological parameters and can be considered an indicator of poor prognosis for cancer malignancies.

Association of a novel antisense lncRNA TP73-AS1 polymorphisms and expression with colorectal cancer susceptibility and prognosis.

TP73-AS1 is a novel antisense long noncoding RNA and plays an important role in cell proliferation and cancer development. However, the link between TP73-AS1 and colorectal cancer (CRC) has not yet been reported. To explore the association of genetic variants in TP73-AS1 and its expression with CRC susceptibility and prognosis. A case-control study (including 507 CRC cases and 503 controls) and bioinformatics analysis were conducted. rs9800 polymorphism was significantly related to higher risk in CRC [adjusted odds ratio (AOR) = 1.33, 95% confidence interval (CI) = 1.02-1.75, P = 0.034 in heterozygote codominant model]. There was no difference between TP73-AS1 polymorphisms and different tumor node metastasis (TNM) stages in the adjusted model. Moreover, TP73-AS1 expression level was positively related to different TNM stages. After adjusted for age, gender and TNM, higher TP73-AS1 expression levels were related to shorter recurrence-free survival time [hazard ratio (HR) = 1.66, 95% CI = 1.02-2.71, P = 0.043]. TP73-AS1 polymorphisms and expression may be associated with susceptibility and prognosis of CRC.

LncRNA TP73-AS1 promotes the development of Epstein-Barr virus associated gastric cancer by recruiting PRC2 complex to regulate WIF1 methylation.

Epstein-Barr virus associated gastric cancer (EBVaGC) become a growing health problem. TP73-AS1 showed high expression in EBVaGC cells. However, the function role and underlying mechanism of TP73-AS1 need further exploration. The expressions of TP73-AS1, WIF1, EZH2, β-catenin and epithelial-mesenchymal transition (EMT)-related proteins were detected using qRT-PCR and Western blotting. Cell proliferation, apoptosis, migration and invasion were measured by CCK-8, colony formation, flow cytometry, wound healing and transwell assays, respectively. WIF1 promoter methylation was analyzed by MS-PCR (MSP). RNA immunoprecipitation assay (RIP) and Chromatin immunoprecipitation assay (ChIP) measured the interactions of TP73-AS1/EZH2 and EZH2/WIF1. Subcutaneous tumor growth was monitored in nude mice and immunohistochemistry (IHC) detected proliferation marker Ki-67 expression. TP73-AS1 was increased while WIF1 was decreased in EBVaGC cells. Silencing of TP73-AS1 or overexpression of WIF1 repressed the growth and migration while promoted apoptosis of EBVaGC cells. Knockdown of WIF1 reversed the anticancer effect of TP73-AS1 silencing. TP73-AS1 promoted the binding of EZH2 to the WIF1 promoter by directly binding to EZH2, and thus inhibiting the expression of WIF1 by enhancing H3K27me3 level of WIF1 promoter. Moreover, TP73-AS1 activated Wnt/β-catenin signaling pathway and promoted EMT by down-regulating WIF1. TP73-AS1 silencing inhibited the progression of EBVaGC in nude mice by epigenetically regulating WIF1. TP73-AS1 regulated the promoter methylation of WIF1 by recruiting PRC2 complex to WIF1 promoter region, thereby promoting the progression of EBVaGC. These observations provided a novel theoretical basis to investigate more effective therapies of EBVaGC.

LncRNA TP73-AS1 promotes oxidized low-density lipoprotein-induced apoptosis of endothelial cells in atherosclerosis by targeting the miR-654-3p/AKT3 axis

BackgroundAlthough lncRNA TP73-AS1 has been shown to play important roles in various human diseases, its function in atherosclerosis (AS) remains unclear.MethodsHuman aortic endothelial cells (HAECs) were treated with 50 μg/ml oxidized low-density lipoprotein (ox-LDL) to establish an atherosclerotic cell model. The expression of TP73-AS1, miR-654-3p and AKT3 was detected by qRT-PCR. Cell functions were evaluated CCK-8 assay and flow cytometry. The protein levels of apoptosis-related proteins were evaluated by western blot. The binding relationship among TP73-AS1, miR-654-3p and AKT3 was determined by bioinformatics analysis and luciferase reporter assay.ResultsTP73-AS1 was upregulated and miR-654-3p was downregulated in ox-LDL treated HAECs. TP73-AS1 silencing and miR-654-3p mimics decreased the viability and inhibited apoptosis of ox-LDL treated HAECs, decreased the expression levels of c-caspase-9, c-caspase-3 and Bax, and increased Bcl-2 expression. In addition, miR-654-3p inhibitor significantly reversed the inhibitory effects of si-TP73-AS1 on cell viability and apoptosis. TP73-AS1 could positively regulate AKT3 through directly sponging miR-654-3p.ConclusionTP73-AS1 promoted apoptosis of ox-LDL stimulated endothelial cells by targeting the miR-654-3p/AKT3 axis, suggesting that TP73-AS1 might be a potential target for AS treatment.

Long non-coding RNA TP73-AS1 promotes pancreatic cancer growth and metastasis through miRNA-128-3p/GOLM1 axis.

BACKGROUNDPrevious studies have suggested that long non-coding RNAs (lncRNA) TP73-AS1 is significantly upregulated in several cancers. However, the biological role and clinical significance of TP73-AS1 in pancreatic cancer (PC) remain unclear. AIMTo investigate the role of TP73-AS1 in the growth and metastasis of PC.METHODSThe expression of lncRNA TP73-AS1, miR-128-3p, and GOLM1 in PC tissues and cells was detected by quantitative real-time polymerase chain reaction. The bioinformatics prediction software ENCORI was used to predict the putative binding sites of miR-128-3p. The regulatory roles of TP73-AS1 and miR-128-3p in cell proliferation, migration, and invasion abilities were verified by Cell Counting Kit-8, wound-healing, and transwell assays, as well as flow cytometry and Western blot analysis. The interactions among TP73-AS1, miR-128-3p, and GOLM1 were explored by bioinformatics prediction, luciferase assay, and Western blot. RESULTSThe expression of TP73-AS1 and miRNA-128-3p was dysregulated in PC tissues and cells. High TP73-AS1 expression was correlated with a poor prognosis. TP73-AS1 silencing inhibited PC cell proliferation, migration, and invasion in vitro as well as suppressed tumor growth in vivo. Mechanistically, TP73-AS1 was validated to promote PC progression through GOLM1 upregulation by competitively binding to miR-128-3p. CONCLUSIONOur results demonstrated that TP73-AS1 promotes PC progression by regulating the miR-128-3p/GOLM1 axis, which might provide a potential treatment strategy for patients with PC.

LncRNA TP73-AS1 enhances the malignant properties of pancreatic ductal adenocarcinoma by increasing MMP14 expression through miRNA -200a sponging.

Pancreatic ductal adenocarcinoma (PDAC) is an invasive and aggressive cancer that remains a major threat to human health across the globe. Despite advances in cancer treatments and diagnosis, the prognosis of PDAC patients remains poor. New and more effective PDAC therapies are therefore urgently required. In this study, we identified a novel host factor, namely the LncRNA TP73‐AS1, as overexpressed in PDAC tissues compared to adjacent healthy tissue samples. The overexpression of TP‐73‐AS1 was found to correlate with both PDAC stage and lymph node metastasis. To reveal its role in PDCA, we targeted TP73‐AS1 using LnRNA inhibitors in a range of pancreatic cancer (PC) cell lines. We found that the inhibition of TP73‐AS1 led to a loss of MMP14 expression in PC cells and significantly inhibited their migratory and invasive capacity. No effects of TP73‐AS1 on cell survival or proliferation were observed. Mechanistically, we found that TP73‐AS1 suppressed the expression of the known oncogenic miR‐200a. Taken together, these data highlight the prognostic potential of TP73‐AS1 for PC patients and highlight it as a potential anti‐PDAC therapeutic target.

LncRNA TP73-AS1 regulates miR-495 expression to promote migration and invasion of nasopharyngeal carcinoma cells through junctional adhesion molecule A.

The main obstacle to the treatment of nasopharyngeal carcinoma (NPC) is metastasis. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are highly involved in the progression of NPC. In this study, we aimed to explore the regulatory role of lncRNA P73 antisense RNA 1 T (TP73-AS1) and miR-495 in migration and invasion of NPC cells. The expression levels of TP73-AS1, miR-495, and junctional adhesion molecule A (JAM-A) in NPC tissue samples and cell lines were examined by quantitative real-time PCR (qRT-PCR) and/or Western blot. NPC cells were transfected with vectors overexpressing TP73-AS1, short hairpin RNA (shRNA) against TP73-AS1, shRNA against JAM-A, miR-495 mimics, miR-495 inhibitor, and their corresponding negative controls as designated. The MTT assay, cell migration assay, and transwell assay were performed to detect cell viability, migration, and invasion, respectively. Dual-luciferase reporter assay was performed to confirm the binding of TP73-AS1 and miR-495, and miR-495 and JAM-A. TP73-AS1 and JAM-A were significantly upregulated while miR-495 was markedly downregulated in NPC tissues and cell lines compared to normal controls. The overexpression of TP73-AS1 promoted migration and invasion of NPC cell line CNE-2. TP73-AS1 targeted miR-495 and negatively regulated its expression. TP73-AS1 upregulated the expression of JAM-A through miR-495. TP73-AS1 mediated migration and invasion of CNE-2 cells via upregulating JAM-A. LncRNA TP73-AS1, miR-495, and JAM-A are involved in migration and invasion of NPC cells. The TP73-AS1/miR-495/JAM-A axis may serve as a therapeutic target for the treatment of NPC.

LncRNA TP73-AS1/miR-539/MMP-8 axis modulates M2 macrophage polarization in hepatocellular carcinoma via TGF-β1 signaling

PurposeOur study aimed to study the role of lncRNA TP73-AS1/miR-539/MMP-8 axis in modulating M2 macrophage polarization in hepatocellular carcinoma (HCC). MethodsThe gene expression levels of TP73-AS1, miR-539 and MMP-8 were modified by transfection with the overexpression or knockdown vectors. The patient survival rate was analyzed using Kaplan-Meier method. The levels of TP73-AS1, miR-539, MMP-8 and M1/2 macrophage polarization markers were analyzed by qRT-PCR, western blot, and flow cytometry. The release of TGF-β1 in the supernatant was determined by ELISA assay. The interaction between TP73-AS1, miR-539 and MMP-8 was analyzed by bioinformatics analysis and dual-luciferase reporter assays. Mouse xenograft model was further established to examine the therapeutic effects of the TP73-AS1 knockdown and miR-539 overexpression in vivo. ResultsWe found TP73-AS1 and MMP-8 upregulation, and miR-539 downregulation in HCC tissues and cell lines. Lower TP73-AS1 and MMP-8 expressions and higher miR-539 expression were associated with higher survival rate of patients. M2-macrophage markers CD206, Arg-1 and CD163 were significantly upregulated in the tumor tissues. TP73-AS1 negatively and directly regulated miR-539 and knockdown of TP73-AS1 inhibited MMP-8 expression and M2 macrophage polarization. Also, overexpression of miR-539 suppressed M2 macrophage polarization by negatively regulating MMP-8. Furthermore, knockdown of MMP-8 also restrained M2 macrophage polarization via inhibiting TGF-β1 signaling. We also found knockdown of TP73-AS1 or overexpression of miR-539 inhibited HCC tumor growth and M2 macrophage infiltration in vivo. ConclusionOur study demonstrated lncRNA TP73-AS1 negatively regulated miR-539 to promote MMP-8 expression, which activated TGF-β1 signaling to induce M2 macrophage polarization in HCC.

Huaier Restrains Cholangiocarcinoma Progression in vitro and in vivo Through Modulating lncRNA TP73-AS1 and Inducing Oxidative Stress.

PurposeHuaier, the fruiting body of Trametes robiniophila Murr, is a kind of traditional Chinese medicine. Recently, many studies have confirmed that Huaier has antitumor effects on various malignancies. Moreover, studies have demonstrated that long noncoding RNAs play an important regulatory role in the occurrence and progression of malignancies. Our present study was to explore whether Huaier has a potential antitumor effect in cholangiocarcinoma and reveal the relationship between lncRNAs and Huaier-induced tumor inhibition.MethodsMicroarray assay was performed to identify the candidate lncRNAs regulated by Huaier. Quantitative real-time PCR was applied to assess the effect of Huaier on TP73-AS1 expression. The effect of Huaier on the cell viability, proliferation, migration and invasion was evaluated by CCK-8, colony formation, wound healing and Transwell assays, respectively. The ratio of cell apoptosis was determined using AO/EB, Hoechst 33342 and flow cytometry. The effect of Huaier on oxidative stress was revealed using DCFH-DA, mito-SOX, JC-1 probes and Western blotting. In addition, the effect of Huaier on tumor growth and metastasis was explored using subcutaneous tumor model and lung metastatic tumor model in nude mice.ResultsIn vitro, Huaier inhibited the proliferation, migration and invasion of cholangiocarcinoma cells by down-regulating TP73-AS1 and induced apoptosis through mitochondrial apoptotic pathway. In vivo, Huaier suppressed the growth and metastasis of cholangiocarcinoma by modulating the expression of proliferation and EMT-associated proteins.ConclusionHuaier could inhibit cell proliferation, invasion and metastasis by modulating the expression of TP73-AS1, meanwhile promote apoptosis of CCA cells through disturbing mitochondrial function, inducing oxidative stress and activating caspases in vitro. In addition, Huaier could suppress tumor growth and metastasis by regulating the expression of proliferation and EMT-related proteins. In the meantime, Huaier prolonged the survival of nude mice in lung metastatic model with acceptable drug safety.

Long non-coding RNA TP73-AS1 contributes to glioma tumorigenesis by sponging the miR-103a/GALNT7 pathway

Glioma is the most aggressive, commonly occurring brain tumor in adults. Long non-coding RNAs (lncRNAs) are among the gene expression regulators in cancer development. Previous research posited that the up-regulation of LncRNA TP73-AS1 (TP73-AS1) in glioma is linked to low survival rates. However, the precise LncRNA TP73-AS1 mechanism in glioma remains unknown. Herein, we found that TP73-AS1 was up-regulated in glioma and was associated with a dismal prognosis. The silencing of TP73-AS1 repressed the multiplication of glioma cells and caused cell death. Mechanistically, we identified that TP73-AS1 in glioma acts as a ceRNA by sequestering miR-103a from GALNT7. Further, the results of this study revealed a reciprocal expression between TP73-AS1 and miR-103a, and a positive regulation between TP73-AS1 and GALNT7, validating the identified mechanism. Besides, luciferase reporter assay identified miR-103a as the direct binding site of both TP73-AS1 and GALNT7. Moreover, the findings of CCK-8 and colony-formation assays indicated that exogenous expression of GALNT7 reversed TP73-AS1-induced division inhibition of glioma cells. Altogether, our results established that TP73-AS1 facilitates the progression of glioma through competing for endogenous RNA (ceRNA) in a TP73-AS1/miR-103a/GALNT7 loop.

LncRNA TP73-AS1 Regulates miR-21/PTEN Axis to Affect Cell Proliferation in Acute Myeloid Leukemia

Objective: TP73-AS1 has been reported as an overexpressed oncogenic lncRNA in several types of cancer. However, these analyses of The Cancer Genome Atlas data set revealed downregulation of TP73-AS1 in acute myeloid leukemia (AML). In this study, we aimed to study the molecular mechanism between TP73-AS1 and cell proliferation in AML. Methods: Bone marrow (BM) samples were obtained from 50 AML patients and 50 healthy controls. Cell transient transfections were performed to analyze gene interactions. Dual-luciferase reporter assay, quantitative polymerase chain reaction and Western blot were used to study the gene expressions. Cell proliferation was analyzed by CCK-8 method. Results: TP73-AS1 was confirmed to be downregulated in AML. TP73-AS1 was predicted to interact with miR-21, while overexpression of TP73-AS1 and miR-21 did not affect the expression of each other. Instead, overexpression of TP73-AS1 led to the upregulation of phosphatase and tensin homologue (PTEN), a downstream target of miR-21. Cell proliferation analysis showed that overexpression of TP73-AS1 and PTEN led to a decreased proliferation rate of AML cells. Overexpression of miR-21 played an opposite role and reduced the effects of overexpressing TP73-AS1 and PTEN. Conclusion: TP73-AS1 may regulate the miR-21/PTEN axis to affect cell proliferation in AML.

Erratum: LncRNA TP73-AS1 Activates TGF-β1 to Promote the Migration and Invasion of Colorectal Cancer Cell [Corrigendum

[This corrects the article DOI: 10.2147/CMAR.S228490.].

LncRNA TP73-AS1 Activates TGF-β1 to Promote the Migration and Invasion of Colorectal Cancer Cell.

PurposeLncRNA TP73-AS1 has been demonstrated to promote the developments of several types of human cancer. However, its role in colorectal cancer (CRC) is unknown.MethodsAll CRC patients (n=70, 40 males and 30 females, 38 to 66 years’ old, 52.1 ± 5.3 years’ old) in this study were enrolled in the Affiliated Hospital of Southwest Medical University from July 2012 to January 2014. Cells, vectors, and transient transfections, RT-qPCR, western-blotting, as well as measurements of cell migration and invasion abilities were carried out during the research.ResultsIn the present study, we found that TP73-AS1 was upregulated in CRC tissues compared with adjacent non-CRC tissues in CRC patients. Upregulation of TP73-AS1 was closely correlated with poor prognosis. TGF-β1 was also upregulated in CRC tissues and positive correlated with TP73-AS1. TP73-AS1 overexpression caused upregulated TGF-β1 in CRC cells, while TGF-β1 overexpression showed no significant effect on TP73-AS1. TP73-AS1 and TGF-β1 overexpressions caused enhanced migration and invasion of CRC cells. TGF-β inhibitor treatment caused suppressed migration and invasion of CRC cells and attenuated effects of TP73-AS1 and TGF-β1 overexpression.ConclusionTherefore, TP73-AS1 may inactivate TGF-β1 to inhibit the migration and invasion of CRC cells.

Knockdown Of Long Non-Coding RNA TP73-AS1 Inhibited Cell Proliferation And Metastasis Through Wnt/β-Catenin Pathway In Lung Adenocarcinoma.

BackgroundVarious evidences showed that abnormally expressed long non-coding RNAs (lncRNAs) play important roles in the tumorigenesis and progression of malignancies. However, the exact role and regulatory mechanism of lncRNA TP73-AS1 in the pathogenesis and progression of lung adenocarcinoma remain to be further elucidated.PurposeThe aim of this study was to investigate the functional role and underlying mechanism of lncRNA TP73-AS1 in lung adenocarcinoma progression.MethodsRT-PCR assay was employed to detect TP73-AS1 expression in lung adenocarcinoma tissues and cells. The function of TP73-AS1 in lung adenocarcinoma progression was estimated by MTT assay, EdU assay, flow cytometry, Western blot, wound-healing assay and transwell assay.ResultsLncRNA TP73-AS1 expression was significantly increased in lung adenocarcinoma tissues and cell lines. Moreover, functional assays revealed that silencing of lncRNA TP73-AS1 could attenuate cell proliferation, migration, invasion and epithelial–mesenchymal transition of lung adenocarcinoma, while enhanced expression of lncRNA TP73-AS1 led to the opposite results. Additionally, lncRNA TP73-AS1 knockdown could facilitate cell apoptosis and overexpression of lncRNA TP73-AS1 inhibited cell apoptosis. In addition, we further determined that lncRNA TP73-AS1 regulated cell metastasis through inducing the activation of Wnt/β-catenin signaling pathway in lung adenocarcinoma.ConclusionOur results indicated that lncRNA TP73-AS1 may play an oncogenic role in lung adenocarcinoma progression, which provided a promising therapy strategy for the treatment of lung adenocarcinoma.

Long Noncoding RNA TP73-AS1 Modulates Medulloblastoma Progression In Vitro And In Vivo By Sponging miR-494-3p And Targeting EIF5A2.

BackgroundPrevious studies have shown that P73 antisense RNA 1T (non-protein coding), also known as TP73-AS1, is a long non-coding RNA (lncRNA) and involved in the development of medulloblastoma. However, the regulatory mechanism of lncRNA TP73-AS1 in medulloblastoma was still unclear, the present study was aimed to investigate the detailed functions and the mechanism of TP73-AS1 in regulation of medulloblastoma.Materials and methodsThe levels of TP73-AS1, miR-494-3p, and Eukaryotic initiation factor 5A2 (EIF5A2) were determined using quantitative real-time PCR (qRT-PCR), in situ hybridization (ISH), or Immunohistochemistry (IHC). The function of TP73-AS1 in proliferation, apoptosis, migration, and invasion of medulloblastoma cells was evaluated using cell counting Kit-8 (CCK-8), flow cytometry, and transwell assay, respectively. The protein levels were determined by Western blot. Bioinformatics analysis and dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and pull-down assay were used to search and confirm the target gene of TP73-AS1 and miR-494-3p. The effect of TP73-AS1 knockdown in vivo was detected by animal experiment.ResultsThe levels of TP73-AS1 and EIF5A2 were up-regulated, while miR-494-3p expression was down-regulated in medulloblastoma tissues and cells, ELF5A2 was a direct target of miR-494-3p, and miR-494-3p bound to TP73-AS1. The knockdown of TP73-AS1 inhibited cell proliferation, invasion, migration, and promoted apoptosis of medulloblastoma cells, while the miR-494-3p inhibitor abolished the effects of TP73-AS1 knockdown on medulloblastoma cells.ConclusionTP73-AS1 positively regulated EIF5A2 expression by sponging miR-494-3p. These findings suggested that TP73-AS1 served as an oncogene and promoted the progression of medulloblastoma.

Long Noncoding RNA TP73-AS1 Targets MicroRNA-329-3p to Regulate Expression of the SMAD2 Gene in Human Cervical Cancer Tissue and Cell Lines.

BackgroundWorldwide, mortality from cervical cancer in women remains high. This study aimed to investigate the expression of long noncoding RNA (lncRNA) TP73-AS1, microRNA-329-3p (miRNA-329-3p), and the SMAD2 gene and their regulatory relationships in human cervical cancer tissue and cervical cancer cell lines.Material/MethodsCervical cancer tissue samples (n=30) and normal control cervical tissues were studied. Cell proliferation and migration were investigated in HeLa and SiHa human cervical cancer cells using the MTT assay, crystal violet staining, wound healing assay, and the transwell assay. Expression of lncRNA TP73-AS1 and the SMAD2 gene were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Enrichment of miR-329-3p was measured using the RNA immunoprecipitation assay (RIPA). Targeting relationships between TP73-AS1, miR-329-3p, and SMAD2 were identified using the dual-luciferase reporter assay. A subcutaneous xenograft model was established, tumor size was measured, and SMAD2 expression was detected using immunohistochemistry.ResultsLncRNA TP73-AS1 was overexpressed in cervical cancer tissues and cells and was associated with reduced expression of miR-329-3p. Down-regulation of lncRNA TP73-AS1 inhibited cell proliferation, migration and invasion and increased miR-329-3p expression. Expression of SMAD2 down-regulated miR-329-3p and was associated with increased expression of TP73-AS1. LncRNA TP73-AS1 knockdown resulted in miR-329-3p silencing. In tumor xenografts, expression of TP73-AS1 reduced the tumor volume and down-regulated the expression levels of the SMAD2 gene.ConclusionsLncRNA TP73-AS1 promoted proliferation of cervical cancer cell lines by targeting miR-329-3p to regulate the expression of the SMAD2 gene. A regulatory network was formed between lncRNA TP73-AS1, miR-329-3p, and SMAD2.

RETRACTED ARTICLE: Down-regulated lncRNA TP73-AS1 reduces radioresistance in hepatocellular carcinoma via the PTEN/Akt signaling pathway

Statement of Retraction We, the Editors and Publisher of the journal Cell Cycle, have retracted the following article: Wei Song, Jingjing Zhang, Qingxin Xia and Miaomiao Sun. Down-regulated lncRNA TP73-AS1 reduces radioresistance in hepatocellular carcinoma via the PTEN/Akt signaling pathway. Cell Cycle. 2019;18(22):3177-3188. doi: 10.1080/15384101.2019.1671089 Since publication, significant concerns have been raised about the integrity of the data and reported results in the article. When approached for an explanation, the authors have been unable to address the concerns raised and have not been able to provide sufficient supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. The authors agree with the retraction. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.