lncRNA HOXA11-AS maintains the stemness of oral squamous cell carcinoma stem cells and reduces the radiosensitivity by targeting miR-518a-3p/PDK1.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) is the most prevailing oral malignancy. The lncRNA HOXA11-AS shows prominent roles in OSCC. This study explored the effects of lncRNA HOXA11-AS on regulating OSCC stem cell stemness and radiosensitivity by targeting miR-518a-3p/PDK1. METHODS: Human OSCC cell lines SCC9 and SCC15 were selected. CD133+ cancer stem cells (CSCs) were sorted by immunomagnetic beads. CD133 expression in cells and HOXA11-AS expression in SCC9, SCC15, and CD133+ SCC9, CD133+ SCC15 cells were assessed by flow cytometry and RT-qPCR. HOXA11-AS was silenced/overexpressed in SCC9, SCC15, CD133+ SCC9, and CD133+ SCC15 cells. Cell proliferation, radiosensitivity, invasion, and stem cell sphere formation ability were examined by CCK-8, colony formation, Transwell, and stem cell sphere formation. The levels of stemness-related genes (Oct4, Nanog, Sox2), miR-518a-3p, epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, Vimentin, N-cadherin), and PDK1 were assessed by RT-qPCR and Western blot assay. RESULTS: HOXA11-AS was up-regulated in SCC9, SCC15, CD133+ SCC9, and CD133+ SCC15 cells. HOXA11-AS silencing inhibited OSCC proliferation and invasion and enhanced radiosensitivity. HOXA11-AS maintained CSC stemness in OSCC. HOXA11-AS silencing reduced CD133+ SCC9 and CD133+ SCC15 stem cell sphere formation ability, reduced stem cell stemness-related gene levels, and inhibited EMT. HOXA11-AS regulated OSCC stem cell stemness and radiosensitivity by targeting miR-518a-3p. PDK1 overexpression annulled the regulatory effects of HOXA11-AS silencing on OSCC cell stem cell stemness and radiosensitivity. CONCLUSION: In vitro lncRNA HOXA11-AS silencing inhibited OSCC stem cell stemness by targeting the miR-518a-3p/PDK1 axis, thus enhancing OSCC cell radiosensitivity.

Increased expression of HOXA11-AS attenuates endometrial decidualization in recurrent implantation failure patients.

Endometrial decidualization is a prerequisite for implantation, and impaired decidualization is associated with recurrent implantation failure (RIF). Coding genes of the HOX family have been clarified as critical regulators in endometrial decidualization, but the role of long non-coding RNAs (lncRNAs) in the HOX gene family has yet to be determined. The aim of this study was to clarify the possible roles of lncRNAs in the HOX gene family in decidualization. In this study, we identified that HOXA11-AS was the most reduced lncRNA in the HOX family in the human endometrium during the window of implantation, and it was elevated in RIF patients. Mechanistically, HOXA11-AS negatively regulated decidualization through competitive interaction with PTBP1, an RNA-binding protein. Binding of PTBP1 to HOXA11-AS limited PTBP1 availability to regulate PKM1/2 alternative splicing, resulting in enhanced PKM1 and diminished PKM2 expression, thus attenuating decidualization. The pattern of high HOXA11-AS expression and impaired PKM2 splicing was consistently observed in RIF patients. Collectively, our study indicates that the increase of HOXA11-AS is detrimental to endometrial decidualization, likely contributing to RIF. Our study may shed light on the pathogenesis and treatment of RIF.

The lncRNA HOXA11-AS acts as a tumor promoter in breast cancer through regulation of the miR-125a-5p/TMPRSS4 axis.

BACKGROUND: Long non-coding RNAs (lncRNAs) play vital roles in tumorigenesis. Here, we explored how lncRNA HOXA11-AS functions in the progression of breast cancer (BC). METHODS: HOXA11-AS and miR-125a-5p levels were measured by a quantitative real-time polymerase chain reaction, whereas western blotting determined TMPRSS4 levels in BC tumor tissues, adjacent normal tissues and BC cell lines. The roles of HOXA11-AS, miR-125a-5p and TMPRSS4 in BC proliferation were investigated using cell counting kit-8, colony formation and flow cytometry assays, whereas scratch and transwell assays were used to measure metastasis. RNA pull-down assays and dual-luciferase assays assessed direct interactions between HOXA11-AS and miR-125a-5p. The effects of HOXA11-AS in vivo were investigated in a BC xenograft model. RESULTS: HOXA11-AS was upregulated in tumor tissues of 56 BC patients compared to adjacent non-tumor tissues, with high levels being associated with worse overall survival. Silencing of HOXA11-AS inhibited the proliferation and metastasis of BC cells, leading to cell cycle arrest in G0/G1 and induction of apoptosis. We identified miR-125a-5p as a target of HOXA11-AS, with miR-125a-5p inhibitors partially restoring the reduction of cell proliferation and metastasis induced by HOXA11-AS silencing. We also determined that miR-125a-5p targeted TMPRSS4 mRNA, with HOXA11-AS knockdown and miR-125a-5p mimics suppressing TMPRSS4. Overexpression of TMPRSS4 partially compensated for the reduction of cell proliferation and metastasis induced by HOXA11-AS silencing. Finally, we confirmed the mechanism of HOXA11-AS in the regulation of tumorigenesis in the mouse model. CONCLUSIONS: HOXA11-AS regulates the tumorigenic ability of BC via the miR-125a-5p/TMPRSS4 axis. This provides insights for regulatory mechanisms involved in BC progression, and may enable new treatment strategies in the clinical setting.

An Axis between the Long Non-Coding RNA HOXA11-AS and NQOs Enhances Metastatic Ability in Oral Squamous Cell Carcinoma.

Long non-coding RNAs (lncRNAs) play critical roles in human cancers. HOXA11 anti-sense RNA (HOXA11-AS) is an lncRNA belonging to the homeobox (HOX) gene cluster that promotes liver metastasis in human colon cancer. However, its role and mechanism of action in human oral squamous cell carcinoma (OSCC) are unclear. In this study, we investigated HOXA11-AS expression and function in human OSCC tissues and cell lines, as well as a mouse model of OSCC. Our analyses showed that HOXA11-AS expression in human OSCC cases correlates with lymph node metastasis, nicotinamide adenine dinucleotide (NAD)(P)H: quinone oxidoreductase 1 (NQO1) upregulation, and dihydronicotinamide riboside (NRH): quinone oxidoreductase 2 (NQO2) downregulation. Using the human OSCC cell lines HSC3 and HSC4, we demonstrate that HOXA11-AS promotes NQO1 expression by sponging microRNA-494. In contrast, HOXA11-AS recruits zeste homolog 2 (EZH2) to the NQO2 promoter to suppress its expression via the trimethylation of H3K27. The upregulation of NQO1 enzymatic activity by HOXA11-AS results in the consumption of flavin adenine dinucleotide (FAD), which reduces FAD-requiring glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity and suppresses glycolysis. However, our analyses show that lactic acid fermentation levels are preserved by glutaminolysis due to increased malic enzyme-1 expression, promoting enhanced proliferation, invasion, survival, and drug resistance. In contrast, suppression of NQO2 expression reduces the consumption of NRH via NQO2 enzymatic activity and increases NAD levels, which promotes enhanced stemness and metastatic potential. In mouse tumor models, knockdown of HOXA11-AS markedly suppressed tumor growth and lung metastasis. From these findings, targeting HOXA11-AS may strongly suppress high-grade OSCC by regulating both NQO1 and NQO2.

The long non-coding RNA HOXA11-AS activates ITGB3 expression to promote the migration and invasion of gastric cancer by sponging miR-124-3p.

BACKGROUND: miR-124-3p can inhibit integrin ß3 (ITGB3) expression to suppress the migration and invasion of gastric cancer (GC), and in the process lncRNA HOXA11-AS may act as a molecular sponge. METHODS: Luciferase reporter assay was conducted to verify the binding of miR-124-3p and HOXA11-AS. RT-PCR and western blot were performed to detect the expression of HOXA11-AS, miR-124-3p and ITGB3 in GC tissues and cells. Gene silence and overexpression experiments as well as cell migration and invasion assays on GC cell lines were performed to determine the regulation of molecular pathways, HOXA11-AS/miR-124-3p/ITGB3. Furthermore, the role of HOXA11-AS in GC was confirmed in mice models. RESULTS: We found HOXA11-AS is up-regulated in GC tissues and can bind with miR-124-3p. Through overexpression/knockdown experiments and function tests in vitro, we demonstrated HOXA11-AS can promote ITGB3 expression by sponging miR-124-3p, consequently enhance the proliferation, migration, and invasion of GC cells. Meanwhile, we validated that HOXA11-AS promotes migration and invasion of GC cells via down-regulating miR-124-3p and up-regulating ITGB3 in vivo. CONCLUSIONS: We demonstrated that lncRNA HOXA11-AS can increase ITGB3 expression to promote the migration and invasion of gastric cancer by sponging miR-124-3p. Our results suggested that HOXA11-AS may reasonably serve as a promising diagnostic biomarker and a potential therapeutic target of GC.

LncRNA HOXA11-AS Aggravates Keloid Progression by the Regulation of HOXA11-AS-miR-205-5p-FOXM1 Pathway.

BACKGROUND: Keloid is troublesome for patients' skin appearance and mental health, although it is a benign tumor. Long noncoding RNA (lncRNA) troubling keloid is frequently reported. The purpose of this study was to investigate the role of lncRNA homeobox (HOX) A11 antisense (HOXA11-AS) and related action mechanisms during the development of keloid. METHODS: The expression of HOXA11-AS, miR-205-5p, and forkhead box M1 (FOXM1) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation or apoptosis was assessed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium (MTT) assay or flow cytometry assay. Cell migration and invasion were monitored by transwell assay. The protein levels of extracellular matrix (ECM) proteins (collagen I and collagen III), fibronectin, glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and FOXM1 were quantified by Western blot. Glycolysis processes were investigated by the glycolysis stress test, glucose consumption, and lactate production. The relationship between miR-205-5p and HOXA11-AS or FOXM1 was predicted by the online tool MIRcode or starBase v2.0 and verified by dual-luciferase reporter assay or RNA immunoprecipitation (RIP). RESULTS: HOXA11-AS and FOXM1 were significantly upregulated in keloid tissues and keloid fibroblasts, while miR-205-5p was downregulated. HOXA11-AS knockdown or miR-205-5p enrichment inhibited proliferation, migration, invasion, ECM accumulation, and glycolysis but accelerated apoptosis of keloid fibroblasts. MiR-205-5p was targeted by HOXA11-AS, and its inhibition overturned the effects of HOXA11-AS knockdown. Moreover, FOXM1 was a target of miR-205-5p, and HOXA11-AS regulated the expression of FOXM1 by adsorbing miR-205-5p. FOXM1 overexpression abolished the role of miR-205-5p enrichment. CONCLUSIONS: The HOXA11-AS-miR-205-5p-FOXM1 pathway may be an active mode in which HOXA11-AS participates in the progression of keloid.

LncRNA HOXA11-AS regulates calcium oxalate crystal-induced renal inflammation via miR-124-3p/MCP-1.

Long noncoding RNA (lncRNA) has been suggested to play an important role in a variety of diseases over the past decade. In a previous study, we identified a novel lncRNA, termed HOXA11-AS, which was significantly up-regulated in calcium oxalate (CaOx) nephrolithiasis. However, the biological function of HOXA11-AS in CaOx nephrolithiasis remains poorly defined. Here, we demonstrated that HOXA11-AS was significantly up-regulated in CaOx nephrolithiasis both in vivo and in vitro. Gain-/loss-of-function studies revealed that HOXA11-AS inhibited proliferation, promoted apoptosis and aggravated cellular damage in HK-2 cells exposed to calcium oxalate monohydrate (COM). Further investigations showed that HOXA11-AS regulated monocyte chemotactic protein 1 (MCP-1) expression in HK-2 cell model of CaOx nephrolithiasis. In addition, online bioinformatics analysis and dual-luciferase reporter assay results showed that miR-124-3p directly bound to HOXA11-AS and the 3'UTR of MCP-1. Furthermore, rescue experiment results revealed that HOXA11-AS functioned as a competing endogenous RNA to regulate MCP-1 expression through sponging miR-124-3p and that overexpression of miR-124-3p restored the inhibitory effect of proliferation, promotion effects of apoptosis and cell damage induced by HOXA11-AS overexpression. Taken together, HOXA11-AS mediated CaOx crystal-induced renal inflammation via the miR-124-3p/MCP-1 axis, and this outcome may provide a good potential therapeutic target for nephrolithiasis.

CTCF-induced upregulation of HOXA11-AS facilitates cell proliferation and migration by targeting miR-518b/ACTN4 axis in prostate cancer.

BACKGROUND: Testified as crucial participators in different types of human malignancies, long noncoding RNAs (lncRNAs) have been revealed to exert a significant effect on the complicated courses of tumor progression. Although existing literatures have revealed the oncogenic role of lncRNA homeobox A11 antisense RNA (HOXA11-AS) in multiple cancers, the underlying role of HOXA11-AS in prostate cancer (PCa) and its potential molecular mechanism remains poorly understood. AIM: To decipher the molecular performance of HOXA11-AS in PCa. METHODS: The expression of HOXA11-AS, miR-518b and actinin alpha 4 (ACTN4) was detected by a real-time quantitative polymerase chain reaction. Colony formation, EdU, flow cytometry, wound healing, and transwell assays were utilized to explore the biological role of HOXA11-AS in PCa. The interaction between RNAs (CCCTC-binding factor [CTCF], HOXA11-AS, miR-518b, and ACTN4) was tested via chromatin immunoprecipitation, luciferase reporter and RNA immunoprecipitation assays. RESULTS: HOXA11-AS in PCa cells was expressed at high levels. Silenced HOXA11-AS in PCa cells could lead to a significant elevation in the abilities of cell proliferation and migration whereas a remarkable declination in cell apoptosis capability. Subsequent molecular mechanism assays confirmed that HOXA11-AS bound with miR-518b and negatively regulates miR-518b expression. Besides, HOXA11-AS could regulate the expression of ACTN4 by sponging miR-518b. Moreover, rescued-function assays revealed that miR-518b inhibition or ACTN4 upregulation reversed the repressive effect of HOXA11-AS knockdown on PCa progression. Furthermore, CTCF was validated to activate HOXA11-AS transcription in PCa cells. CONCLUSIONS: CTCF-induced upregulation of HOXA11-AS facilitates PCa progression via miR-518b/ACTN4 axis, providing a new target for PCa treatment.

Propofol promotes apoptosis of colorectal cancer cells via alleviating the suppression of lncRNA HOXA11-AS on miRNA let-7i.

To date, surgical resection is the mainstay for the treatment of colorectal cancer (CRC). Propofol (2,6-diisopropylphenol), one of the most commonly used intravenous anaesthetic agents, has been reported to be involved in modulating the malignancy of a variety of human cancers. However, the underlying mechanisms remain poorly understood. In this study, using a cell counting kit (CCK-8), flow cytometry, and caspase-3 cleavage assays, we found that propofol promoted cell apoptosis and inhibited cell proliferation in both Colo205 and SW620 cells, through the down-regulation of HOXA11-AS and up-regulation of let-7i. Moreover, gain-of-function studies of HOXA11-AS or loss-of-function studies of let-7i also revealed a negative correlation between HOXA11-AS and let-7i in propofol-mediated biological functions of CRC cells. Furthermore, our mechanistic experiments revealed that HOXA11-AS acts as a molecular sponge for let-7i, thereby regulating the expression of ABCC10. We investigate the theory that propofol suppresses colorectal cancer tumorigenesis by modulating the HOXA11-AS-let-7i-ABCC10 regulatory network, indicating the potential for propofol to control CRC development.

Long non-coding RNA HOXA11-AS induces type I collagen synthesis to stimulate keloid formation via sponging miR-124-3p and activation of Smad5 signaling.

Keloid, characterized by exuberant collagen deposition and invasive growth beyond original wound margins, results from abnormal wound healing. A recent microarray analysis identified homeobox (HOX) A11 antisense (HOXA11-AS) as a keloid-specific long non-coding RNA, although its potential role in keloid formation remains elusive. In this study, hematoxylin-eosin, Masson, and immunohistochemical staining of type I collagen (ColI) revealed abnormal arrangement and hyperplasia of fibers in keloid tissues along with increased ColI level. qRT-PCR and Western blot showed that HOXA11-AS and ColI were significantly upregulated, while miR-124-3p was decreased in both keloid tissues and human keloid fibroblasts (HKFs). Knockdown of HOXA11-AS inhibited cell proliferation (by CCK-8 and immunofluorescence staining of Ki67) and cell migration (by wound healing and transwell assays). Mechanistic experiments verified that HOXA11-AS acted as a sponge of micro-RNA (miR)-124-3p and Smad5 was a target of miR-124-3p. miR-124-3p sufficiently reversed the regulatory effects of HOXA11-AS, and Smad5 was involved in miR-124-3p-mediated biological functions. Furthermore, HOXA11-AS induced ColI synthesis via sponging miR-124-3p-mediated Smad5 signaling, thus promoting keloid formation. Overall, our study implied that HOXA11-AS induces ColI synthesis to promoted keloid formation via sponging miR-124-3p-mediated Smad5 signaling, which might offer a novel target for developing the therapy of keloid formation.

HOXA11-AS promotes the progression of oral squamous cell carcinoma by targeting the miR-518a-3p/PDK1 axis.

BACKGROUND: Long non-coding RNAs (lncRNAs) are promising therapeutic molecules of cancer. Here we aim to study the therapeutic effect and mechanism of a lncRNA, HOXA11-AS, in oral squamous cell carcinoma (OSCC). METHODS: OSCC tissues and adjacent matched paraneoplastic normal tissues used in this study were collected from 42 OSCC patients. The significant downregulation or upregulation of HOXA11-AS expression in OSCC cells was confirmed by quantitative real-time PCR (qRT-PCR). Bioinformatics analysis of StarBase were performed to investigate the potential microRNAs mediated by HOXA11-AS. HOXA11-AS-transfected cells or control cells were subcutaneously injected into nude mice to further determine the effects of HOXA11-AS on OSCC progression in vivo. RESULTS: qRT-PCR analysis indicated that HOXA11-AS expression was significantly upregulated in OSCC tissues. Functional studies revealed that HOXA11-AS significantly promotes cell proliferation, reduces the percentage of G0/G1 phase cells and enhances the cell invasion in OSCC. Bioinformatics analysis suggested that a microRNA (miRNA), miR-518a-3p, is as a target of HOXA11-AS. Alteration of miR-518a-3p levels by HOXA11-AS transduced to changes in PDK1 expression. In a mouse model of OSCC, HOXA11-AS overexpression promoted tumor growth, concomitant with reduced miR-518a-3p expression and increased PDK1 expression. CONCLUSION: Taken together, our study demonstrates that HOXA11-AS/miR-518a-3p/PDK1 axis is an important regulator of OSCC progression and may serve as a potential therapeutic target in OSCC. HARMU20150128, registered at Jan, 28 2018.

LncRNA HOXA11-AS promotes hepatocellular carcinoma progression by repressing miR-214-3p.

Accumulating studies supported that lncRNAs played important roles in tumorigenesis. LncRNA HOXA11-AS was a novel lncRNA that has been proved to involved in several tumours. However, the role of HOXA11-AS in the development of hepatocellular carcinoma (HCC) remains to be explained. In our study, we showed that HOXA11-AS expression was up-regulated in the HCC tissues, and the higher expression of HOXA11-AS was associated with the advanced stage in the HCC samples. In addition, we indicated that the expression of HOXA11-AS was up-regulated in HCC cell lines (Hep3B, SMMC-7721, MHCC97-H and BEL-7402) compared with normal liver cell lines (HL-7702). Overexpression of HOXA11-AS promoted HCC proliferation and invasion and induced the epithelial-mesenchymal transition (EMT) and knockdown of HOXA11-AS suppressed the HCC cell proliferation and invasion. However, we showed that miR-214-3p expression was down-regulated in the HCC tissues and cell lines. Ectopic expression of miR-214-3p suppressed HCC cell proliferation and invasion. Furthermore, we indicated that overexpression of HOXA11-AS decreased the miR-214-3p expression and the expression of miR-214-3p was negatively related with the HOXA11-AS expression in HCC samples. Ectopic expression of HOXA11-AS increased HCC proliferation and invasion and induced EMT through inhibiting miR-214-3p expression. These data suggested that HOXA11-AS/miR-214-3p axis was responsible for development of HCC.

HOXA11-AS promotes the growth and invasion of renal cancer by sponging miR-146b-5p to upregulate MMP16 expression.

Recently, increasing studies showed that long noncoding RNAs (lncRNAs) play critical roles in tumor progression. However, the function and underlying mechanism of HOMEOBOX A11 antisense RNA (HOXA11-AS) on renal cancer remain unclear. In the current study, our data showed that the expression of HOXA11-AS was significantly upregulated in clear cell renal cell carcinoma (ccRCC) tissues and cell lines. High HOXA11-AS expression was associated with the advanced clinical stage, tumor stage, and lymph node metastasis. Function assays showed that HOXA11-AS inhibition significantly suppressed renal cancer cells growth, invasion, and ETM phenotype. In addition, underlying mechanism revealed that HOXA11-AS could act as a competing endogenous RNA (ceRNA) that repressed miR-146b-5p expression, which regulated its downstream target MMP16 in renal cancer. Taken together, our findings suggested that HOXA11-AS could promote renal cancer cells growth and invasion by modulating miR-146b-5p-MMP16 axis. Thus, our findings suggested that HOXA11-AS could serve as potential therapeutic target for the treatment of renal cancer.

LncRNA HOXA11-AS drives cisplatin resistance of human LUAD cells via modulating miR-454-3p/Stat3.

Over the past several years, long non-coding RNAs (lncRNAs) have attracted more and more attention due to their special functions. They are vital biomarkers in multiple diseases. LncRNA HOMEOBOX A11 (HOXA11) has been found to be aberrantly expressed in some kinds of malignant tumors. In this study, we mainly discuss the oncogenic role of it in promoting malignant progression and chemoresistance in lung adenocarcinoma (LUAD) cells. The expression of HOXA11-AS was much stronger in cisplatin-resistant LUAD cells. Based on The Cancer Genome Atlas database, patients with high expression of HOXA11-AS had shorter survival time. Additionally, knockdown of HOXA11-AS caused positive changes in cell activities of LUAD. For example, cell proliferation and migration were weakened, the epithelial mesenchymal transition process was reversed, and apoptosis was induced. These changes were more obvious in cells treated with cisplatin. Next, the HOXA11-AS/miR-454-3p/Stat3 (signal transducer and activator of transcription 3) pathway was found to influence the cisplatin resistance of LUAD cells. HOXA11-AS specifically acted as a competing endogenous RNA (ceRNA) in LUAD cells. The combinations among these three genes were demonstrated. Finally, rescue assays were applied to demonstrate the ceRNA pattern consisting of HOXA11-AS, miR-454-3p and Stat3. In conclusion, lncRNA HOXA11-AS acted as a ceRNA to promote cisplatin resistance of human LUAD cells via the miR-454-3p/Stat3 axis.

Effect of lncRNA HOXA11-AS1 on adipocyte differentiation in human adipose-derived stem cells.

AIMS: To determine the role of lncRNA HOXA11-AS1 on adipocyte differentiation. METHODS: Human adipose-derived stem cells (hADSCs) were isolated from adipose tissues of patients and cultured in vitro, followed by knockdown of HOXA11-AS1. Then, adipocyte differentiation and expression of adipogenic-related genes (CEBP-α, DGAT2, CIDEC, and perilipin) were measured by RT-qPCR and Western blot. RESULTS: We demonstrated that knockdown of HOXA11-AS1 inhibited adipocyte differentiation, leading to suppression of adipogenic-related gene (CEBP-α, DGAT2, CIDEC, and perilipin) transcription, as well as decreased lipid accumulation in hADSCs. In addition, lncRNA HOXA11-AS1 was highly expressed in obese patients and significantly increased during the process of adipocyte differentiation. CONCLUSION: The results provide new insight into the molecular mechanism by which lncRNA HOXA11-AS1 is involved in adipogenesis and may have implications for the treatment of obesity and associated disorders.

Prognostic and clinicopathological significance of long noncoding RNA HOXA11-AS expression in human solid tumors: a meta-analysis.

BACKGROUND: Recent studies have emphasized the important prognostic role of long noncoding RNAs (lncRNAs) in various types of cancers. Here we conducted a meta-analysis to investigate whether lncRNA HOXA11-AS can be served as a prognostic biomarker in human cancers. PATIENTS/METHODS: We systematically searched PubMed, Embase, ISI Web of Science, and SCOPUS for relevant studies, to investigate the prognostic significance of HOXA11-AS expression in cancer patients. Odds ratios (ORs) or hazards ratios (HRs) with corresponding 95% confidence intervals (CIs) are pooled to estimate the association between HOXA11-AS expression and clinicopathological parameters or survival of cancer patients. RESULTS: A total of eight eligible studies with 1320 cancer patients were enrolled in our meta-analysis. The results revealed that increased expression level of HOXA11-AS was significantly associated with clinicopathological parameters including more lymph node metastasis (OR = 2.06, 95% CI 1.31-3.25), advanced tumor stage (OR = 4.22, 95% CI 2.60-6.85), as well as poor tumor differentiation (OR = 2.49, 95 CI 1.47-4.20), but not correlated with age (p = 0.101) or gender (p = 0.845). In addition, cancer patients with high HOXA11-AS are prognosed to have shorter OS (pooled HR = 1.86, 95% CI 1.39-2.48) and PFS (pooled HR = 2.47, 95% CI 1.29-4.75). CONCLUSIONS: HOXA11-AS overexpression might be a convinced unfavorable prognostic factor that helps the clinical decision-making process.

The role of the long non-coding RNA HOXA11-AS in promoting proliferation and metastasis of malignant tumors.

Long non-coding RNA (lncRNA) is one of the focuses and hotspots of biological research in recent years. At the same time, tumors have become the main disease that endangers human health. In recent years, a large number of researchers have explored the relationship between lncRNA and tumors. HOXA11-AS is one of these lncRNAs. The long non-coding RNA HOXA11 antisense RNA (HOXA11-AS) is a novel lncRNA recently discovered. It is found in a variety of tumors such as ovarian cancer, glioma, and gastric cancer (GC) and so on, and is defined as an oncogene. It promotes tumor proliferation and metastasis by interacting with proteins such as miRNA and EZH2. In this paper, we review the mechanism of interaction between HOXA11-AS and various tumors in recent years, and believe that it can be a potential tumor marker and therapeutic target in the future prevention and treatment of tumors.

Long non-coding RNA homeobox (HOX) A11-AS promotes malignant progression of glioma by targeting miR-124-3p.

Glioma is the most common and serious form of primary tumor in adult central nervous system. HOXA11-AS is a LncRNA located in the HOXA gene cluster. In the present study, we investigated the expression and function of LncRNA HOXA11-AS in glioma tissues and cells. We found that LncRNA HOXA11-AS expression was markedly elevated in glioma tissues compared to normal brain tissues. The LncRNA HOXA11-AS expression in cases of high-grade glioma was significantly higher than that in cases of low-grade. Patients with high LncRNA HOXA11-AS expression had shorter OS time than those with low LncRNA HOXA11-AS expression. Moreover, silencing LncRNA HOXA11-AS inhibited cell proliferation, increased apoptosis, and inhibited invasion and migration of glioma cells. Overexpression of LncRNA HOXA11- AS increased cell proliferation, decreased apoptosis, and increased invasion and migration of glioma cells. miR-124-3p has relevant binding sites in HOXA11-AS. Silencing HOXA11-AS significantly increased miR-124-3p expression. The miR-124-3p overexpression decreased the luciferase activity of the pMIR luciferase reporter containing HOXA11-AS-WT but not HOXA11-AS-MUT. Moreover, miR-124-3p was pulled down by HOXA11-AS probe. miR-124-3p mimics inhibited cell proliferation, increased apoptosis, and inhibited invasion and migration of glioma cells. miR-124-3p mimics significantly suppressed overexpression of HOXA11-AS-induced increase of proliferation, decrease of apoptosis and increase of invasion and migration. miR-124-3p inhibitors suppressed the effect of siHOXA11-AS on proliferation, apoptosis, invasion and migration. In summary, the findings highlight the importance of LncRNA HOXA11-AS/miR-124-3p axis in the regulation of glioma progression. LncRNA HOXA11-AS/miR-124-3p might serve as a potential therapeutic target in glioma treatment in the future.

[Expression level and clinical significance of LncRNA HOXA11-AS in esophageal squamous cell carcinoma patients].

Objective: To explore the expression of long noncoding RNA (lncRNA) HOXA11-AS in esophageal squamous cell carcinoma tissues and the relationship of HOXA11-AS level with clinical outcomes. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression level of HOXA11-AS in cell lines HET-1A, EC9706, EC109, and in tumor tissue and paired adjacent tissue samples from 73 ESCC patients who received surgical resection.The correlations of the expression level of HOXA11-AS with clinicopathological features and prognosis were also analyzed. Results: The relative expression levels of HOXA11-AS in tumor tissue and paired adjacent tissue were 0.832±0.387 and 2.486±1.087, respectively, with significant difference (P<0.001). The expression of HOXA11-AS was upregulated in 63.0%(46/73)ESCC tissues. The relative expression levels of HOXA11-AS in HET-1A, EC-9706 and EC-109 cells were 1.000, 23.553±3.221 and 17.217±1.968, respectively. The expression level of HOXA11-AS was upregulated in ESCC cell lines (P<0.001). High expression level of HOXA11-AS was correlated with histological grade and lymph node metastasis of ESCC patients (P<0.05). However, it was not associated with the age, gender, depth of infiltration and TNM staging (P>0.05). The median overall survival (OS) and median disease-free survival (DFS) of patients with low HOXA11-AS expression were 43 months and 42 months, respectively, significantly longer than 37 months and 28 months of patients with HOXA11-AS high expression (P<0.05). Cox model multivariate analysis showed that the expression of HOXA11-AS and lymph node metastasis were independent factors of poor prognosis of ESCC patients. Conclusions: The expression of HOXA11-AS is upregulated in esophageal cancer cell lines and tissues. High expression of HOXA11-AS is associated with poor prognosis of ESCC patients.Therefore, LncRNA HOXA11-AS may serve as a predictive marker of postoperative ESCC patients.