lncRNA Biomarkers of Glioblastoma Multiforme.

Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14-16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients' blood.

Downregulation of long noncoding RNA TP73-AS1 expression confers resistance to temozolomide in human glioblastoma cells.

Glioblastoma multiforme (GBM), the most aggressive primary malignant brain tumor, is resistant to conventional radiotherapies and chemotherapies, including temozolomide (TMZ). Overcoming GBM resistance to the chemotherapeutic agent TMZ poses an important therapeutic problem. This study established an association between the long noncoding RNA TP73-AS1 and TMZ sensitivity regulation in human GBM cells (U87MG). Transcriptomic analysis revealed that TP73-AS1 expression was reduced in TMZ-resistant U87MGRT100 cells compared to that in parental U87MG cells. Additionally, TP73-AS1 knockdown in parental U87MG cells decreased their sensitivity to TMZ. Overall, these findings suggest that TP73-AS1 functions as a regulator of TMZ sensitivity in GBM cells.

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.

Circulating TP73-AS1 and CRNDE serve as diagnostic and prognostic biomarkers for non-small cell lung cancer.

BACKGROUND: Circulating long noncoding RNAs (lncRNAs) are considered a new class of biomarkers for the diagnosis and prognosis of various malignancies. We aimed to identify circulating lncRNAs as biomarkers for the diagnosis and prognosis of non-small cell lung cancer (NSCLC). METHODS: The expression of 14 candidate lncRNAs was measured in matched cancer and ipsilateral normal lung tissues of 20 patients with NSCLC using quantitative reverse-transcription PCR. In plasma samples from training and testing sets, significantly and aberrantly expressed lncRNAs, TA73-AS1 and CRNDE, were further analyzed. Receiver operating characteristic (ROC) curves were constructed, and the areas under the ROC curves (AUC) were obtained to assess diagnostic performance. The Kaplan-Meier survival analysis was used to assess the impact of plasma TA73-AS1 and CRNDE expression on tumor-free survival (TFS) of patients with NSCLC. The effect of TP73-AS1 expression on NSCLC cells was investigated in vitro. RESULTS: AUC values of plasma TA73-AS1 and CRNDE were 0.822 and 0.815 in the training set and 0.843 and 0.804 in the testing set, respectively, to distinguish NSCLC from healthy controls. The combination of plasma TP73-AS1, CRNDE, and two classical tumor markers, carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1), showed excellent diagnostic performance for NSCLC (AUC =0.927 in the training set; AUC = 0.925 in the testing set). Furthermore, the high expression of the two plasma lncRNAs correlated with worse TFS in patients with NSCLC. In vitro cell model studies revealed that TP73-AS1 overexpression facilitated NSCLC cell survival, invasion, and migration. CONCLUSION: Circulating TP73-AS1 and CRNDE could be potential biomarkers for the diagnosis and prognostic prediction of NSCLC.

Long non-coding RNA tumor protein 73 antisense RNA 1 influences an interaction between lysine demethylase 5A and promoter of tumor protein 73 to enhance the malignancy of colorectal cancer.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. The aim of the present study was to explore the expression level of tumor protein 73 (TP73) in highly malignant CRC tumors and how the long non-coding RNA tumor protein 73 antisense RNA 1 (TP73-AS1) influences that transcription. We found that TP73-AS1 was highly expressed in malignant CRC samples in The Cancer Genome Atlas (TCGA) database. We also demonstrated TP73-AS1 was expressed in thirty samples of CRC tissues collected from China Medical University patients as well as in HCT116, RKO and SW480 CRC cell lines but not in HCoEpiC or CCD-18Co normal colon cells. Only wild-type TP73-AS1, but not any of its alternate splicing isoforms, was positively correlated with tumor malignancy. TP73-AS1 transcripts were shown to be located in cell nuclei especially in close proximity to the TP73 promoter in CRC cells, but not in normal colon cells. In addition, an interaction between lysine demethylase 5A (KDM5A) and TP73-AS1 in CRC cells, but not normal colon cells, and KDM5A localization on the TP73 promoter were influenced by TP73-AS1. Interestingly, the H3K4me3 level on the TP73 promoter was reduced, but was elevated by TP73-AS1 knockdown in CRC cells. In conclusion, these results suggest a novel epigenetic role of TP73-AS1 on histone demethylation that influences TP73 transcription, and shed light on malignancy in CRC.

miR-320a promotes p53-dependent apoptosis of prostate cancer cells by negatively regulating TP73-AS1 invitro.

TP73 antisense RNA 1 (TP73-AS1) is an oncogenic long non-coding RNA that is activated in several types of cancers. It has been shown that the activity of TP73-AS1 is controlled by several miRNAs, but post-transcriptional mechanisms that regulate TP73-AS1 activity in prostate cancer remain highly elusive. Accordingly, in the present study, we aimed to determine the miRNAs that are involved in the regulation of TP73-AS1 in prostate cancer and to show the effects of these molecules on the malignant proliferation of prostate cancer cells. Remarkably, colony formation and cell migration were suppressed while cell cycle arrest and apoptosis were induced in prostate cancer cells overexpressing miR-200a and miR-320a. miR-200a and miR-320a were found to be upregulated in TP73-AS1 suppressed prostate cancer cells. Also, TP73-AS1 was shown to be downregulated following miR-200a and miR-320a overexpression. However, overexpression of miR-320a had no significant effect on the expression of TP73. Further analysis revealed that miR-320a induces p53-dependent apoptosis. Consequently, our findings indicate that miR-320a induces p53-dependent apoptosis by negatively regulating TP73-AS1 long non-coding RNA.

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

BACKGROUND: Long 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. METHODS: We 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. RESULTS: A 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. CONCLUSIONS: The upregulation of Lnc RNA TP73-AS1 was related to detrimental clinicopathological parameters and can be considered an indicator of poor prognosis for cancer malignancies.

TP73-AS1 promotes gastric cancer proliferation and invasion by regulation miR-27b-3p/TMED5 axis.

Background: Gastric cancer (GC) is a common gastrointestinal malignancy. Evidence suggests that long non-coding RNAs (lncRNAs) influence mRNA expression to induce GC progression. We aim to investigate the function and regulatory mechanism of TP73-AS1 in GC. Materials and methods: We detected TP73-AS1, miR-27b-3p, and TMED5 (Transmembrane P24 Trafficking Protein 5) by real-time polymerase chain reaction (RT-PCR). Similarly, the protein levels of TMED5 and wnt/ß-catenin were detected by western-blot. The colony formation and Cell-Counting Kit-8 (CCK-8) assay detected cell proliferation. Transwell and scrape assay tested cell migration and invasion. Dual-luciferase reporter assays confirmed directed binding targets. Tumor xenograft in nude mice checked the result in vivo. Results: TP73-AS1 over-expressed in GC. Suppressed TP73-AS1 inhibited cell proliferation, migration, and invasion. However, down-regulated miR-27b-3p could reverse the effects of weakenTP73-AS1 on the progression of GC. Moreover, TMED5 was also up-regulated in GC. Both TP73-AS1 and TMED5 were the direct target of miR-27b-3p. Meanwhile, miR-27b-3p was a negative correlation with TP73-AS1 and TMED5. The TP73-AS1/miR-27b-3p/TMED5 axis regulate wnt/ß-catenin pathway. Conclusion: TP73-AS1 promoted GC proliferation, migration, and invasion by sponging miR-27b-3p to regulate TMED5. TP73-AS1 was a potential onco-lncRNA in GC.

Long non-coding RNA TP73-AS1 predicts poor prognosis and regulates cell proliferation and migration in cervical cancer.

Introduction: Cervical cancer is one of the most common malignant tumors in women, which seriously affects women's health, especially in developing countries. This study aims to investigate novel molecular markers for poor prognosis of cervical cancer to achieve correct guidance of clinical treatment, accurate assessment of prognosis, and provide a new basis for the choice of reasonable treatment options for cervical cancer patients. Material and methods: QRT-PCR was employed to investigate the expression of lncRNA TP73-AS1 in cervical cancer tissues and cell lines. COX multivariate analysis showed the relationship between TP73-AS1 expression and clinicopathological features of patients with cervical cancer. Colony formation and MTT assay detected the effect of TP73-AS1 on proliferation of cervical cancer cells. The effect of TP73-AS1 on migration and invasion of cervical cancer cells was determined by the wound-healing assay and transwell assay. Western blot was performed to assess the expression of EMT markers. Results: This study showed that lncRNA TP73-AS1 was up-regulated in cervical cancer tissues and cell lines (p < 0.001), and high expression of TP73-AS1 could be considered as an independent prognostic factor (p < 0.05). Moreover, lncRNA TP73-AS1 promotes cervical cancer cell migration and invasion, and knockdown of TP73-AS1 inhibits the growth of cervical cancer cells (p < 0.001). Conclusions: Our results indicated that lncRNA TP73-AS1 was up-regulated in cervical cancer tissues and cell lines, predicting poor prognosis of cervical cancer and regulating cell proliferation and migration.

Silencing of TP73-AS1 impairs prostate cancer cell proliferation and induces apoptosis via regulation of TP73.

BACKGROUND: Prostate cancer is a malignant disease that severely affects the health and comfort of the male population. The long non-coding RNA TP73-AS1 has been shown to be involved in the malignant transformation of various human cancers. However, whether TP73-AS1 contributes to prostate cancer progression has not been reported yet. Accordingly, here we aimed to report the role of TP73-AS1 in the development and progression of prostate cancer and determine its relationship with TP73. METHODS AND RESULTS: TP73-AS1-specific siRNA oligo duplexes were used to silence TP73-AS1 in DU-145 and PC-3 cells. Results indicated that TP73-AS1 was upregulated whereas TP73 was downregulated in prostate cancer cells compared to normal prostate cells and there was a negative correlation between them. Besides, loss of function experiments of TP73-AS1 in prostate cancer cells strongly induced cellular apoptosis, interfered with the cell cycle progression, and modulated related pro- and anti-apoptotic gene expression. Colony formation and migration capacities of TP73-AS1-silenced prostate cancer cells were also found to be dramatically reduced. CONCLUSIONS: Our findings provide novel evidence that suggests a chief regulatory role for the TP73-TP73-AS1 axis in prostate cancer development and progression, suggesting that the TP73/TP73-AS1 axis can be a promising diagnostic and therapeutic target for prostate cancer.

LncRNA TP73-AS1 promotes nasopharyngeal carcinoma progression through targeting miR-342-3p and M2 polarization via exosomes.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a deadly cancer, mainly presenting in southeast and east Asia. Long noncoding RNAs (lncRNAs) play essential roles in cancer progression. Exosomes are critical for intercellular communication. Thus, the aim of this study was to identify the functional lncRNAs in NPC and its relevant mechanisms. METHODS: Data from public databases were utilized to screen for functional lncRNAs in NPC. Functional and mechanical experiments were performed to determine the role of lncRNAs in NPC and its relative molecular mechanisms. Exosomes derived from NPC cells were isolated to determine their function in tumor-associated macrophages. RESULTS: LncRNA TP73-AS1 was increased in NPC cells and tissues and was associated with a poor prognosis. TP73-AS1 overexpression promoted proliferation, colony formation, and DNA synthesis of NPC cells while TP73-AS1 knockdown showed opposite roles. TP73-AS1 could directly bind with miR-342-3p. MiR-342-3p overexpression attenuated the effect of TP73-AS1 in NPC cells. Furthermore, TP73-AS1 was transferred by exosomes to promote M2 polarization of macrophages. Lastly, exosomal TP73-AS1 enhanced the motility and tube formation of macrophages. CONCLUSIONS: Together, this study suggests that TP73-AS1 promotes NPC progression through targeting miR-342-3p and exosome-based communication with macrophages and that TP73-AS1 might be an emerging biomarker for NPC.

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

BACKGROUND: 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. OBJECTIVE: To explore the association of genetic variants in TP73-AS1 and its expression with CRC susceptibility and prognosis. METHODS: A case-control study (including 507 CRC cases and 503 controls) and bioinformatics analysis were conducted. RESULTS: 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]. CONCLUSION: 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.

BACKGROUND: 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. METHODS: The expressions of TP73-AS1, WIF1, EZH2, ß-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. RESULTS: 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/ß-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. CONCLUSION: 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.

BACKGROUND: Although lncRNA TP73-AS1 has been shown to play important roles in various human diseases, its function in atherosclerosis (AS) remains unclear. METHODS: Human 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. RESULTS: TP73-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. CONCLUSION: TP73-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.

BACKGROUND: Previous 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. AIM: To investigate the role of TP73-AS1 in the growth and metastasis of PC. METHODS: The 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. RESULTS: The 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. CONCLUSION: Our 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.

Long non-coding RNA TP73-AS1 is a potential immune related prognostic biomarker for glioma.

Glioma is one of the most common primary brain tumors, and is divided into low-grade and high-grade gliomas. Long non-coding RNAs have been increasingly implicated in the pathogenesis and prognosis of glioma. Here, we demonstrated that the long non-coding RNA TP73-AS1 is differentially expressed among gliomas with different clinicopathological features in The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and GEO glioma datasets; high expression of TP73-AS1 was associated with poor clinical features, including age, stage, IDH mutation status, 1p/19q co-deletion status and overall survival. Measuring TP73-AS1 expression using real-time PCR showed the same result for 76 glioma tissue samples from our hospital. The infiltration levels of various immune cells in the tumor microenvironment were found to be significantly higher in patients with high expression of TP73-AS1. Taken together, our results suggest that TP73-AS1 has potential as a prognostic glioma biomarker. Moreover, the knowledge that TP73-AS1 affects the glioma immune microenvironment may provide new information for the immunological research and treatment of glioma.

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 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.

Long Non-Coding RNA TP73-AS1 Promotes the Development of Lung Cancer by Targeting the miR-27b-3p/LAPTM4B Axis.

PURPOSE: Long non-coding RNA P73 antisense RNA 1T (TP73-AS1) is a newly discovered lncRNA involved in the occurrence and development of several cancers. However, its role in lung cancer has not been well investigated yet. METHODS: The expressions of TP73-AS1, microRNA-27b-3p (miR-27b-3p) and lysosomal-associated protein transmembrane-4 Beta (LAPTM4B) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The cell proliferation, apoptosis, migration and invasion were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Annexin V-FITC/PI and transwell assays, respectively. Tumor xenografts were applied to explore the role of TP73-AS1 in vivo. The target relationship was predicted by StarBase v.2.0 or TargetScan and confirmed by luciferase reporter assay. Pearson's coefficient assay was applied to assess the expression correlation between two groups. Protein expression levels were detected by Western blot. RESULTS: We found that TP73-AS1 was strikingly up-regulated in lung cancer tissues and cells. TP73-AS1 depletion inhibited the growth and metastasis of lung cancer cells in vitro. Furthermore, TP73-AS1 could act as an endogenous sponge by directly binding miR-27b-3p, and a notable inverse correlation between them was also discovered. Importantly, knockdown of miR-27b-3p could reverse the inhibitory effects of TP73-AS1 depletion on the growth and metastasis of lung cancer cells. Besides, LAPTM4B was directly targeted by miR-27b-3p and could be co-regulated by TP73-AS1 and miR-27b-3p in lung cancer cells. Silencing TP73-AS1 hampered tumor growth by regulating miR-27b-3p/LAPTM4B axis in vivo. CONCLUSION: TP73-AS1 promoted the progression of lung cancer through regulating miR-27b-3p/LAPTM4B axis and it might be a potential target for diagnosis and treatment of lung cancer.