HOXA Cluster Antisense RNA 2 Research Articles

HOXA-AS2 Epigenetically Inhibits HBV Transcription by Recruiting the MTA1-HDAC1/2 Deacetylase Complex to cccDNA Minichromosome.

Persistent transcription of HBV covalently closed circular DNA (cccDNA) is critical for chronic HBV infection. Silencing cccDNA transcription through epigenetic mechanisms offers an effective strategy to control HBV. Long non-coding RNAs (lncRNAs), as important epigenetic regulators, have an unclear role in cccDNA transcription regulation. In this study, lncRNA sequencing (lncRNA seq) is conducted on five pairs of HBV-positive and HBV-negative liver tissue. Through analysis, HOXA-AS2 (HOXA cluster antisense RNA 2) is identified as a significantly upregulated lncRNA in HBV-infected livers. Further experiments demonstrate that HBV DNA polymerase (DNA pol) induces HOXA-AS2 after establishing persistent high-level HBV replication. Functional studies reveal that HOXA-AS2 physically binds to cccDNA and significantly inhibits its transcription. Mechanistically, HOXA-AS2 recruits the MTA1-HDAC1/2 deacetylase complex to cccDNA minichromosome by physically interacting with metastasis associated 1 (MTA1) subunit, resulting in reduced acetylation of histone H3 at lysine 9 (H3K9ac) and lysine 27 (H3K27ac) associated with cccDNA and subsequently suppressing cccDNA transcription. Altogether, the study reveals a mechanism to self-limit HBV replication, wherein the upregulation of lncRNA HOXA-AS2, induced by HBV DNA pol, can epigenetically suppress cccDNA transcription.

Helicobacter pylori infection induces gastric cancer cell malignancy by targeting HOXA-AS2/miR-509-3p/MMD2 axis.

Helicobacter pylori (Hp) infection is considered to be the strongest risk factor for gastric cancer (GC). Long non-coding RNA HOXA cluster antisense RNA 2 (HOXA-AS2) has been indicated to be significantly related to Hp infection in GC patients. To investigate the detailed role and molecular mechanism of lncRNA HOXA-AS2 in Hp-induced GC. GC cells were treated with Hp filtrate for cell infection. Bioinformatics tools were utilized for survival analysis and prediction of HOXA-AS2 downstream molecules. Western blotting and RT-qPCR were utilized for assessing protein and RNA levels, respectively. Flow cytometry, colony formation and CCK-8 assays were implemented for testing HOXA-AS2 functions in Hp-infected GC cells. HOXA-AS2 localization in cells was determined by subcellular fractionation assay. The relationship between RNAs were measured by luciferase reporter assay. Hp infection induced HOXA-AS2 upregulation in GC cells. Knocking down HOXA-AS2 restrained cell proliferation but promoted cell apoptosis with Hp infection. HOXA-AS2 bound to miR-509-3p, and miR-509-3p targeted monocyte to macrophage differentiation associated 2 (MMD2). Overexpressing MMD2 reversed HOXA-AS2 depletion-mediated suppression on cell aggressiveness with Hp infection. Hp infection induces the aggressiveness of GC cells by regulating HOXA-AS2/miR-509-3p/MMD2 axis.

Long non-coding HOXA-AS3 contributes to osteosarcoma progression through the miR-1286/TEAD1 axis

Long non-coding RNA (lncRNA) HOXA cluster antisense RNA 3 (HOXA-AS3) regulates the progression of several types of human malignancy. However, the role and potential mechanism of HOXA-AS3 in osteosarcoma (OS) remain unknown. In this study, upregulation of HOXA-AS3 was observed in OS tissues and cell lines and associated with poor clinical outcomes. Silencing of HOXA-AS3 significantly inhibited the proliferation, migration and invasion of OS cells in vitro and suppressed the tumorigenesis of OS cells in vivo. Furthermore, knockdown of HOXA-AS3 inhibited the proliferation and migration of human umbilical vein endothelial cells (HUVECs) and epithelial-to-mesenchymal transition (EMT) in OS. Further investigation of this mechanism revealed that HOXA-AS3 could directly upregulate the expression of TEAD1 via its competing endogenous RNA (ceRNA) activity on miR-1286. This study clarified the oncogenic roles of the HOXA-AS3/miR-1286/TEAD1 axis in OS progression, suggesting a novel therapeutic target for OS.

Assessment of the prognostic and clinicopathological significance of HOXA-AS2 in human cancers: a systematic review and meta-analysis.

Numerous studies have reported that abnormally HOXA cluster antisense RNA 2 (HOXA-AS2) expression plays a critical role in various cancers. Thus, we performed this meta-analysis to comprehensively evaluate the prognostic value of HOXA-AS2 in human cancers. Databases, including PubMed, Web of Science, Embase, China National Knowledge Infrastructure, and Wanfang Data, were searched to retrieve articles on HOXA-AS2 and the prognosis of cancer patients, which were then screened. The association between HOXA-AS2 and overall survival (OS) and the clinicopathological characteristics of patients with cancers were assessed using hazard ratios (HRs) and odds ratios (ORs) combined with 95% confidence intervals (CIs). A subgroup analysis and the Begg test were used to assess the risk of bias of the included studies. Data from The Cancer Genome Atlas (TCGA) were analyzed to verify the results, and the potential regulation mechanism of HOXA-AS2 in cancers was revealed by an immune analysis. A total of 17 articles, comprising 1,176 patients, were included in this meta-analysis. The results showed that high HOXA-AS2 expression was associated with worse OS, advanced tumor node metastasis (TNM) stage, larger tumor size, lymph node metastasis, and distant metastasis in cancer patients but was not related to age, sex, or poor histological grade. The results of the analysis of TCGA data further supported our findings. Additionally, the immune analysis revealed that the expression of HOXA-AS2 was associated with immune cell infiltration and various immune checkpoints. In summary, our results suggest that the high expression of HOXA-AS2 is associated with poor prognosis and the clinicopathological characteristics of cancer patients; thus, it could serve as a prognosis biomarker and therapeutic target for various cancers. However, the small sample size of this study and the inclusion of participants of a single race might have affected the generalizability of our findings. Thus, large-sample, multicenter studies need to be conducted to further evaluate the prognostic role of HOXA-AS2.

HOXA‑AS3 induces tumor progression through the epithelial‑mesenchymal transition pathway in epithelial ovarian cancer.

HOXA cluster antisense RNA 3 (HOXA‑AS3) is considered to be involved in several malignancies, however, its biological function in the progression of epithelial ovarian cancer (EOC) remains unclear. The present study compared the expression of HOXA‑AS3 in ovarian cancer and normal ovarian tissues and analyzed the association between the expression of HOXA‑AS3 and the survival outcomes of patients with ovarian cancer. RNA interference was used to suppress HOXA‑AS3 expression in ovarian cancer cell lines in order to demonstrate the function of HOXA‑AS3 in ovarian cancer progression. The associations between HOXA‑AS3 and epithelial‑mesenchymal transition (EMT) markers were explored to verify the mechanism of action of HOXA‑AS3 in ovarian cancer. The results of the present study revealed that ovarian cancer tissues exhibited higher HOXA‑AS3 expression than normal ovarian tissues. Clinical data indicated that HOXA‑AS3 was a significant predictor of progression‑free survival and overall survival. Patients with high HOXA‑AS3 expression had a poorer prognosis than patients with low HOXA‑AS3 expression. Invitro experiments using HOXA‑AS3‑knockdown ovarian cancer cell lines demonstrated that HOXA‑AS3 knockdown inhibited cell proliferation and migration. HOXA‑AS3 was a potent inducer and modulator of the expression of EMT pathway‑related markers and interacted with both the mRNA and protein forms of HOXA3. Collectively, the findings of the present study demonstrated that HOXA‑AS3 expression is associated with ovarian cancer progression and thus, may be employed as a prognostic marker and therapeutic target in EOC.

Prognostic value of lncRNA HOXA-AS3 in cervical cancer by targeting miR-29a-3p and its regulatory effect on tumor progression.

With the promotion of human papillomavirus (HPV) vaccine, cervical cancer has become a current research hotspot, and lncRNA has been confirmed to be used in the research of different diseases. This article systematically expounds the regulation and potential mechanisms of HOXA cluster antisense RNA 3 (HOXA-AS3) in cervical cancer, and discusses its possibility as a prognostic biomarker for cervical cancer. Relative expression levels of HOXA-AS3 and miR-29a-3p in tissues and cells were determined by real-time quantitative polymerase chain reaction (RT-qPCR). The survival of cervical cancer patients was analyzed by Kaplan-Meier method and the cumulative survival function table was drawn. The proliferation, migration, and invasion levels of HOXA-AS3 in cells were detected according to cell counting kit-8 (CCK-8) and transwell method. The dual-luciferase reporter gene assay confirmed the mechanism of action between HOXA-AS3 and miR-29a-3p. HOXA-AS3 was elevated and miR-29a-3p was decreased in tissues and cells of cervical cancer patients. Knockdown of HOXA-AS3 could inhibit the progression of cervical cancer and was more conducive to patient survival. Bioinformatics analysis confirmed that HOXA-AS3 negatively regulates cervical cancer development by sponging miR-29a-3p. In this research, knockdown of HOXA-AS3 could alleviate the process of cervical cancer by sponging miR-29a-3p, suggesting that HOXA-AS3 may be a potential prognostic target of cervical cancer, which could provide a theoretical basis for future clinical research of cervical cancer.

HOXA cluster antisense RNA 2 elevates KIAA1522 expression through microRNA-520d-3p and insulin like growth factor 2 mRNA binding protein 3 to promote the growth of vascular smooth muscle cells in thoracic aortic aneurysm.

Recently, long non-coding RNAs (lncRNAs) have been revealed to mediate smooth muscle dysfunction in thoracic aortic aneurysm (TAA). LncRNA HOXA-AS2 has been proposed to engage in the regulation of diverse diseases. However, its function in TAA remains unknown. This study aimed to reveal the role and mechanism of HOXA-AS2 in VSMCs which were implicated in TAA formation. RT-qPCR or western blot was performed to detect RNA or protein expression levels. The role of HOXA-AS2 in VSMCs was explored by functional assays. The relationship among HOXA-AS2/miR-520d-3p/KIAA1522/IGF2BP3 was analysed via mechanism assays. HOXA-AS2 was detected to have significantly high expression in TAA tissues and function as an oncogene to promote proliferation of VSMCs, while inhibiting cell apoptosis (Figure 1, **P<0.01). HOXA-AS2 was unveiled to bind with miR-520d-3p (Figure 2, *P<0.05, **P<0.01) and further up-regulate KIAA1522 to facilitate the growth of VSMCs (Figure 3-4, *P<0.05, **P<0.01). HOXA-AS2 was also found to recruit IGF2BP3 to stabilize KIAA1522 mRNA (Figure 5, **P<0.01). All data were displayed as mean±standard deviation. HOXA-AS2 up-regulates KIAA1522 through targeting miR-520d-3p/IGF2BP3 to drive VSMC growth in TAA.

Knocking Down lncRNA HOXA-AS2 Mitigates the Progression of Epilepsy via Regulation of the miR-372-3p/STAT3 Axis.

To explore the potential activity of HOXA cluster antisense RNA 2 (HOXA-AS2), a long non-coding RNA (lncRNA), in epilepsy progression, as well as the mechanisms behind its activity. Kainic acid (KA) was used to treat rat astroglial CTX-TNA2 cells to establish a cellular model of epilepsy. Reverse transcription-quantitative PCR was conducted to examine the expression levels of HOXA-AS2, microRNA (miR)-372-3p and STAT3. Cell Counting Kit-8, flow cytometry and western blot assays were performed to analyze cell viability and apoptosis. The secretion levels of various inflammatory factors (IL-6, IL-1? and TNF-?) were identified by ELISA. To validate the functional interaction between HOXA-AS2/STAT3 and miR?372-3p, dual-luciferase reporter assay was performed. The HOXA-AS2 and STAT3 expression levels were notably upregulated, whereas miR?372-3p was downregulated in KAtreated CTX-TNA2 cells. Silencing HOXA-AS2 or overexpressing miR-372-3p inhibited the secretion of inflammatory factors and apoptosis in KA-treated CTX-TNA2 cells. HOXA-AS2 negatively regulated miR?372-3p, and miR?372-3p targeted STAT3 mRNA. Suppression of miR-372-3p or overexpression of STAT3 abrogated the rescue effect of small interfering HOXA-AS2 in KA-treated CTX-TNA2 cells. The current study suggested that targeting HOXA-AS2 could alleviate cellular damages in the epileptic model by regulating the miR-372-3p/STAT3 axis. Therefore, HOXA-AS2 may serve as a potential anti-epilepsy therapeutic target.

Long Noncoding RNA HOXA Cluster Anti-Sense RNA 2 Inhibits Mycoplasma pneumoniae-Induced Inflammation by Regulating the Nuclear Factor-KappaB Signaling Pathway

Mycoplasma pneumoniae (MP) is the primary cause of community-acquired lung inflammation. The MP-induced manifestations of pneumonia are associated with the release of pro-inflammatory cytokines; however, the mechanisms of MP-induced inflammation have not been fully clarified. The purpose of the present study was to determine whether long noncoding RNA HOXA cluster anti-sense RNA 2 (lncRNA HOXA-AS2) is involved in MP-induced inflammation. A model of MP-induced cellular inflammation was established using the human BEAS-2B lung epithelial cell line and lncRNA HOXA-AS2 levels were detected using reverse transcription-quantitative (RT-q) PCR. MTT and flow cytometric analysis were used to assess cell viability and apoptosis, respectively. The secretion of pro-inflammatory factors including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were measured by ELISA, and protein levels of phosho- (p-)p65 and p-NF-κB inhibitor α (p-IκBα) were detected by western blotting. The results suggest that MP infection significantly decreases the level of lncRNA HOXA-AS2 in BEAS-2B cells. lncRNA HOXA-AS2 overexpression significantly enhanced cell viability, inhibited apoptosis, decreased pro-inflammatory factor expression (TNF-α, IL-β and IL-6) and inhibited NF-κB pathway activation in MP-stimulated BEAS-2B cells. Conversely, lncRNA HOXA-AS2-knockdown resulted in the opposite effects. In conclusion, lncRNA HOXA-AS2 is involved in MP infection-induced inflammation and regulates the NF-κB signaling pathway.

LncRNA HOXA-AS2 Activates the Notch Pathway to Promote Cervical Cancer Cell Proliferation and Migration

Long non-coding RNAs (lncRNAs) are crucial participants in cancer development. HOXA cluster antisense RNA 2 (HOXA-AS2) plays a tumor promoter role in bladder cancer. However, the functional role of HOXA-AS2 in cervical cancer remains unclear. Our study first found that HOXA-AS2 expression was up-regulated in cervical cancer cells. Then functional analysis including cell counting kit-8 (CCK-8), colony formation, transwell, and wound healing uncovered that reduction of HOXA-AS2 remarkably impeded cell proliferation and migration in cervical cancer. Additionally, luciferase reporter assays were performed to confirm that HOXA-AS2 activated Notch signaling pathway via the mediation of independent recombination signal binding protein for JK (RBP-JK) activity. As we know, Notch intracellular domain (NICD) is associated with RBP-JK in the nucleus to promote target genes in the Notch pathway. Through RNA immunoprecipitation (RIP), RNA pull down, and fluorescent in situ hybridization (FISH) assays, we observed that HOXA-AS2 combined with NICD. Moreover, the data from Co-IP assays indicated that HOXA-AS2 reduction weakened the interaction of NICD and RBP-JK. Collectively, HOXA-AS2 played a cancer-promoting role in cervical cancer development by modulating the Notch pathway, which might become a novel target for cervical cancer treatment.

LncRNA HOXA-AS3 Promotes the Progression of Pulmonary Arterial Hypertension through Mediation of miR-675-3p/PDE5A Axis.

Pulmonary arterial hypertension (PAH) seriously threatens the elder people. Long non-coding RNAs (lncRNAs) are involved in multiple diseases. However, the study of the lncRNAs in the occurrence of PAH is just beginning. For this, we sought to explore the biological function of lncRNA HOXA cluster antisense RNA 3 (HOXA-AS3) in PAH. Hypoxia (HYP) was used to mimic in vitro model of PAH. Gene and protein expressions in cells were detected by q-PCR and Western blotting, respectively. In addition, cell proliferation and viability were tested by CCK-8 and MTT assay. Cell apoptosis was measured by flow cytometry. Wound healing was used to detect cell migration. Furthermore, the connection of HOXA-AS3, miR-675-3p, and phosphodiesterase 5A (PDE5A) was verified by dual-luciferase report assay. HOXA-AS3 and PDE5A were upregulated in human pulmonary artery smooth muscle cells (HPASMCs) in the presence of HYP, while miR-675-3p was downregulated. Moreover, knockdown of HOXA-AS3 suppressed the growth and migration of HPASMCs, but induced the apoptosis. Overexpression of miR-675-3p achieved the same effect. MiR-675-3p inhibitor or overexpression of PDE5A notably reversed the inhibitory effect of HOXA-AS3 knockdown on PAH. Finally, HOXA-AS3 could sponge miR-675-3p, and PDE5A was directly targeted by miR-675-3p. HOXA-AS3 increased the development of PAH via regulation of miR-675-3p/PDE5 axis, which could be the potential biomarker for treatment of PAH.

Comprehensive investigation of the clinical significance of long non-coding RNA HOXA-AS2 in acute myeloid leukemia using genome-wide RNA sequencing dataset.

Objective: The present study aimed to determine the prognostic value of HOXA cluster antisense RNA2 (HOXA-AS2) in acute myeloid leukemia (AML), and to explore its potential molecular mechanisms. We also screening of potential drugs targeting HOXA-AS2 in AML.Methods: The level 3 raw genome-wide RNA sequencing dataset of AML was download from The Cancer Genome Atlas (TCGA) Data Portal, and the potential molecular mechanisms and drugs prediction of HOXA-AS2 in AML were explored using multiple bioinformatics analysis approaches.Results: TCGA AML cohort dataset indicated that HOXA-AS2 was significantly up-regulated in AML bone marrow tissues, and high HOXA-AS2 expression was related to poor overall survival (log-rank P=0.0284, hazard ratio 1.640, 95% confidence interval 1.046-2.573). Functional enrichment of differentially expressed genes (DEGs) suggested that the difference in prognosis between AML patients with high- and low-HOXA-AS2 expression may be due to differences in biological processes and pathways, including cell adhesion, angiogenesis, mitogen-activated protein kinase, cell differentiation, and other biological processes, and phosphatidylinositol 3 kinase-protein kinase B and Wnt signaling pathways. We also screened out three potential HOXA-AS2-targeted therapeutic drugs for AML, megestrol, carmustine, and cefoxitin, based on these DEGs. Functional enrichment analysis of HOXA-AS2-co-expressed genes revealed that HOXA-AS2 may act a part in AML by regulating nuclear factor-κB transcription factor activity, DNA methylation, angiogenesis, apoptosis, cell migration, Toll-like receptor 4, and Wnt signaling pathways.Conclusion: Our findings suggest that HOXA-AS2 is up-regulated in the bone marrow in patients with AML, and may serve as a novel prognostic biomarker for AML.

Long noncoding RNA HOXA-AS2 functions as an oncogene by binding to EZH2 and suppressing LATS2 in acute myeloid leukemia (AML)

Acute myeloid leukemia (AML) is the most common hematological malignancy in the world. Long noncoding RNAs (lncRNAs) play an important role in the development of physiology and pathology. Many reports have shown that lncRNA HOXA cluster antisense RNA 2 (HOXA-AS2) is a carcinogen and plays an important role in many tumors, but little is known about its role in AML. The aim of this study was to explore the potential mechanism and role of HOXA-AS2 in AML. HOXA-AS2 was upregulated in AML cell lines and tissues, and the overexpression of HOXA-AS2 is negatively correlated with the survival of patients. Silencing HOXA-AS2 can inhibit the proliferation and induce differentiation of AML cells in vitro and in vivo. Overexpressing HOXA-AS2 showed the opposite result. Moreover, more in-depth mechanism studies showed that carcinogenicity of HOXA-AS2 exerted mainly through binding with the epigenetic inhibitor Enhancer of zeste homolog 2 (EZH2) and then inhibiting the expression of Large Tumor Suppressor 2 (LATS2). Taken together, our findings highlight the important role of HOXA-AS2 in AML, suggesting that HOXA-AS2 may be an effective therapeutic target for patients with AML.

Microarray Analysis of Long Non-Coding RNAs in Lung Tissues of Patients with COPD and HOXA-AS2 Promotes HPMECs Proliferation via Notch1.

Background and ObjectivesLong non-coding RNAs (lncRNAs) play an important role in the pathogenesis of many diseases, including cancer, pulmonary fibrosis and chronic obstructive pulmonary disease (COPD). In this study, we intended to identify the differentially expressed lncRNAs and the role of HOXA cluster antisense RNA 2 (HOXA-AS2) in patients with COPD.MethodsWe analyzed lncRNA profiles of three non-COPD and seven COPD patients’ lungs via microarray and then validated the expression of the top differentially expressed lncRNAs by using real-time polymerase chain reaction (PCR). To identify the mechanism of HOXA-AS2 during COPD pathogenesis and endothelial cell proliferation, we knocked down and overexpressed HOXA-AS2 with siRNA and lentivirus transfection approach in human pulmonary microvascular endothelial cells (HPMECs).ResultsAmong 29,150 distinct lncRNA transcripts, 353 lncRNAs were significantly (≥2-fold change and P<0.05) upregulated and 552 were downregulated in COPD patients. The fold change of HOXA-AS2 is 9.32; real-time PCR confirmed that HOXA-AS2 was downregulated in COPD patients. In in vitro experiments, cigarette smoke extract (CSE) treatment reduced the expression of HOXA-AS2 and cell proliferation of HPMECs. Knocking down HOXA-AS2 inhibited HPMECs proliferation and the expression of Notch1 in HPMECs. Overexpressing Notch1 could partly rescue the inhibition of cell viability induced by the silence of HOXA-AS2.ConclusionOur results demonstrated that differentially expressed lncRNAs may act as potential molecular biomarkers for the diagnosis of COPD, and HOXA-AS2 was involved in the pathogenesis of COPD by regulating HPMECs proliferation via Notch1, which may provide a new approach for COPD treatment.

Long non-coding RNA HOXA-AS2 promotes the expression levels of hypoxia-inducible factor-1α and programmed death-ligand 1, and regulates nasopharyngeal carcinoma progression via miR-519.

Nasopharyngeal carcinoma (NPC) is a rare malignancy arising from the nasopharyngeal epithelium and belongs to the group of head and neck cancer types, which are usually associated with viral and/or environmental influences, as well as heredity causes. A recent study reported that the long non-coding RNA (lncRNA) HOXA cluster antisense RNA 2 (HOXA-AS2) may be a prognostic biomarker in NPC; however, the specific mechanisms underlying NCP progression are yet to be determined. The aim of the present study was to investigate the biological role of HOXA-AS2 in NPC. In the present study, the gene expression levels of HOXA-AS2, miR-519, hypoxia-inducible factor (HIF-1α) and programmed death-ligand 1 (PD-L1) were detected using reverse transcription-quantitative PCR (RT-qPCR) analysis and western blotting. Bioinformatics analysis and a dual luciferase reporter assay were performed to predict and confirm the direct interactions between HOXA-AS2 and microRNA (miR)-519, as well as between miR-519 and HIF-1α. A MTT assay was used to detect the cell viability, while cell migratory and invasive abilities were assessed using wound healing and Transwell assays. HOXA-AS2 and HIF-1α were found to be significantly upregulated in NPC tumor tissues, as well as in NPC cell lines. The overexpression of HOXA-AS2 significantly enhanced NPC progression, including the cell proliferative, migratory and invasive abilities. HOXA-AS2 was identified to directly bind to miR-519, whereas a miR-519 inhibitor significantly rescued the HOXA-AS2 knockdown-attenuated progression of NPC. Moreover, miR-519 could bind to HIF-1α and PD-L1. Overexpression of HIF-1α and PD-L1 significantly promoted NPC progression and partially recovered the phenotype of NPC cells attenuated by HOXA-AS2 knockdown. In conclusion, the present study demonstrated that HOXA-AS2/miR-519/HIF-1α and/or HOXA-AS2/miR-519/PD-L1 may be a novel mechanism regulating the progression of NPC, which may facilitate the development of targeted clinical therapy.

LncRNA HOXA-AS2 promotes the progression of prostate cancer via targeting miR-509-3p/PBX3 axis.

Long non-coding RNAs (lncRNAs) act as crucial modulators during the development of diverse cancers. Although various types of lncRNAs in prostate cancer (PCa) have been explored, quantities of lncRNAs still wait to be exploited. The present study is to probe the functions and mechanism of lncRNA HOXA cluster antisense RNA 2 (HOXA-AS2) in PCa. In the present study, we discovered that HOXA-AS2 was highly expressed in PCa tissues and cells. HOXA-AS2 depletion obviously influenced cell proliferation, migration, invasion, as well as epithelial-to-mesenchymal transition (EMT) progression. In addition, miR-509-3p had low expression in PCa cells and inversely modulated by HOXA-AS2. Cutting down HOXA-AS2 expression was capable of up-regulating miR-509-3p expression. In addition, HOXA-AS2 served as a competing endogenous RNA (ceRNA) through sponging miR-509-3p to release pre-B-cell leukemia homeobox 3 (PBX3) expression. The expression of PBX3 was noticeably high in tumor tissues. And PBX3 expression level was down-regulated markedly with the knockdown of HOXA-AS2. Rescue experiments certified the facilitated role of HOXA-AS2-miR-509-3p-PBX3 axis in regulating the progress of PCa. The present study may provide clues for exploration of novel therapeutic targets for PCa patients.

Long noncoding RNA HOXA-AS2 mediates microRNA-106b-5p to repress sepsis-engendered acute kidney injury.

HOXA cluster antisense RNA 2 (HOXA-AS2) is a long noncoding RNA associated with the development of numerous cancers. But, whether HOXA-AS2 exhibits a certain function in sepsis-engendered acute kidney injury (AKI) remains uninvestigated. We strived to unveil the role of HOXA-AS2 in sepsis-engendered AKI. The expression of HOXA-AS2 in sepsis patients, animal models and lipopolysaccharide (LPS)-impaired HK-2 cells was primarily assessed via a real-time quantitative polymerase chain reaction. The effects of HOXA-AS2 on cell survival of HK-2 cells under LPS irritation were evaluated after overexpression of HOXA-AS2. The correlation between HOXA-AS2 and microRNA (miR)-106b-5p was forecasted via bioinformatics software and verified by using a luciferase report system. Subsequently, the functions of miR-106b-5p in LPS-damaged HK-2 cells were reassessed. Western blot was used for the determination of Wnt/β-catenin and nuclear factor-κB (NF-κB) pathways. HOXA-AS2 expression was decreased in sepsis patients, animal operation group and LPS-irritated HK-2 cells. Overexpressed HOXA-AS2 mollified LPS-triggered impairment in HK-2 cells. In addition, a negative mediatory relation between HOXA-AS2 and miR-106b-5p was predicated. Synchronously, overexpressed miR-106b-5p counteracted the protection of HOXA-AS2 in LPS-damaged HK-2 cells. Ultimately, Wnt/β-catenin and NF-κB pathways were hindered by HOXA-AS2 via targeting miR-106b-5p. HOXA-AS2 exhibited protection in sepsis-engendered AKI via targeting miR-106b-5p and hindering the Wnt/β-catenin and NF-κB pathways.

Long noncoding RNA HOXA-AS2 acts as an oncogene by targeting miR-145-3p in human non-small cell lung cancer.

Recent studies have proved that long non-coding RNAs (lncRNAs) play important roles in many diseases, especially malignancies. The aim of this study was to investigate the exact role of lncRNA HOXA-AS2 (Hoxa cluster antisense RNA 2) in the development of non-small cell lung cancer (NSCLC). Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was utilized to detect HOXA-AS2 expression in NSCLC patients. The Wound healing assay and transwell assay were conducted to explore the function of HOXA-AS2 on NSCLC metastasis. Furthermore, the mechanism assays were used to explore the interaction between HOXA-AS2 and microRNA-145-3p (miR-145-3p). HOXA-AS2 expression level in NSCLC tissues was significantly higher than adjacent tissues. HOXA-AS2 expression was negatively correlated with disease-free survival of NSCLC patients. Moreover, the functional assays showed that the migration and invasion of NSCLC cells were significantly inhibited after HOXA-AS2 in vitro silence. Furthermore, the luciferase reporter gene assay also revealed that miR-145-3p was a direct target of HOXA-AS2 in NSCLC. Our results indicated that HOXA-AS2 could enhance the migration and invasion abilities of NSCLC by targeting miR-145-3p. Furthermore, these findings suggested that HOXA-AS2 might be a potential therapeutic target for NSCLC.

Long Non-Coding RNA HOXA-AS2 Enhances The Malignant Biological Behaviors In Glioma By Epigenetically Regulating RND3 Expression.

IntroductionLong non-coding RNAs (LncRNAs) have been demonstrated to play a vital role in human carcinogenesis. HOXA cluster antisense RNA 2 (HOXA-AS2), a 1048-bp lncRNA located between the HOXA3 and HOXA4 genes, is identified as an oncogene in several malignancies, including glioma. However, the biological functions of HOXA-AS2 and its underlying molecular mechanisms in glioma progression remain to be investigated.MethodThe expression of HOXA-AS2 and RND3 mRNA was determined using qRT-PCR analysis. The protein level of RND3 and EZH2 was measured by Western blot analysis. The biological function of HOXA-AS2 or RND3 in glioma was detected by CCK-8 assay, colony formation assays, transwell assay, and flow cytometry. Dual-luciferase reporter, RIP, RNA-protein pull down and ChIP assays were performed to explore the molecular mechanism of HOXA-AS2 in glioma. The effect of HOXA-AS2 in vivo was examined using xenograft tumor assay.ResultsHOXA-AS2 expression was increased in glioma tissues and cells. High HOXA-AS2 expression was associated with larger tumor size and advanced pathological stage. Functionally, knockdown of HOXA-AS2 suppressed cell proliferation and invasion, and promoted apoptosis. Mechanically, HOXA-AS2 epigenetically inhibited RND3 transcription by binding to EZH2. Moreover, overexpression of RND3 exerted similar tumor-suppressive effects to the depletion of HOXA-AS2. Furthermore, the anti-cancer effects induced by si-HOXA-AS2 were greatly reversed by silencing of RND3. Finally, knockdown of HOXA-AS2 impaired tumor growth in vivo possibly via increasing RND3 expression.ConclusionTaken together, HOXA-AS2 recruits EZH2 to the promoter region of RND3 and inhibits its expression, thereby facilitating glioma progression. Our findings provide a prospective therapeutic strategy for glioma intervention.

Long noncoding RNA HOXA-AS2 promotes non-small cell lung cancer progression by regulating miR-520a-3p.

Background: The HOXA cluster antisense RNA 2 (HOXA-AS2) has recently been discovered to be involved in carcinogenesis in multiple cancers. However, the role and underlying mechanism of HOXA-AS2 in non-small cell lung cancer (NSCLC) yet need to be unraveled. Methods: HOXA-AS2 expression in NSCLC tissues and cell lines was detected using quantitative real-time PCR (qRT-PCR). Furthermore, the effects of HOXA-AS2 on NSCLC cell proliferation, apoptosis, migration, and invasion were assessed by MTS, flow cytometry, wound healing and transwell invasion assays, respectively. Starbase2.0 predicted and luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the association of HOXA-AS2 and miR-520a-3p in NSCLC cells. Results: Our results revealed that HOXA-AS2 in NSCLC tissues were up-regulated and cell lines, and were associated with poor prognosis and overall survival. Further functional assays demonstrated that HOXA-AS2 knockdown significantly inhibited NSCLC cell proliferation, induced cell apoptosis and suppressed migration and invasion. Starbase2.0 predicted that HOXA-AS2 sponge miR-520a-3p at 3′-UTR, which was confirmed using luciferase reporter and RIP assays. miR-520a-3p expression was inversely correlated with HOXA-AS2 expression in NSCLC tissues. In addition, miR-520a-3p inhibitor attenuated the inhibitory effect of HOXD-AS2-depletion on cell proliferation, migration and invasion of NSCLC cells. Moreover, HOXA-AS2 could regulate HOXD8 and MAP3K2 expression, two known targets of miR-520a-3p in NSCLC. Conclusion: These findings implied that HOXA-AS2 promoted NSCLC progression by regulating miR-520a-3p, suggesting that HOXA-AS2 could serve as a therapeutic target for NSCLC.