Quercetin improves epithelial regeneration from airway basal cells of COPD patients.

BACKGROUND: Airway basal cells (BC) from patients with chronic obstructive pulmonary disease (COPD) regenerate abnormal airway epithelium and this was associated with reduced expression of several genes involved in epithelial repair. Quercetin reduces airway epithelial remodeling and inflammation in COPD models, therefore we examined whether quercetin promotes normal epithelial regeneration from COPD BC by altering gene expression. METHODS: COPD BC treated with DMSO or 1 µM quercetin for three days were cultured at air/liquid interface (ALI) for up to 4 weeks. BC from healthy donors cultured at ALI were used as controls. Polarization of cells was determined at 8 days of ALI. The cell types and IL-8 expression in differentiated cell cultures were quantified by flow cytometry and ELISA respectively. Microarray analysis was conducted on DMSO or 1 µM quercetin-treated COPD BC for 3 days to identify differentially regulated genes (DEG). Bronchial brushings obtained from COPD patients with similar age and disease status treated with either placebo (4 subjects) or 2000 mg/day quercetin (7 subjects) for 6 months were used to confirm the effects of quercetin on gene expression. RESULTS: Compared to placebo-, quercetin-treated COPD BC showed significantly increased transepithelial resistance, more ciliated cells, fewer goblet cells, and lower IL-8. Quercetin upregulated genes associated with tissue and epithelial development and differentiation in COPD BC. COPD patients treated with quercetin, but not placebo showed increased expression of two developmental genes HOXB2 and ELF3, which were also increased in quercetin-treated COPD BC with FDR < 0.001. Active smokers showed increased mRNA expression of TGF-ß (0.067) and IL-8 (22.0), which was reduced by 3.6 and 4.14 fold respectively after quercetin treatment. CONCLUSIONS: These results indicate that quercetin may improve airway epithelial regeneration by increasing the expression of genes involved in epithelial development/differentiation in COPD. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov on 6-18-2019. The study number is NCT03989271.

Homeobox B2 promotes malignant behavior and contributes to the radioresistance of nasopharyngeal carcinoma by regulating forkhead box protein O1.

Background: Nasopharyngeal carcinoma (NPC) is an epithelial tumor of the head and neck with heterogeneous racial and geographical distributions. Homeobox B2 (HOXB2) is a tumor promoter in many cancers. However, the biological role of HOXB2 in NPC has not been elucidated. Methods: Bioinformatics analysis was performed to identify the differentially expressed genes (DEGs) between samples of patients with radiosensitive and radioresistant NPC. qRT-PCR, western blotting and immunohistochemistry were used to detect the expression levels of the corresponding mRNA and proteins. Cell viability was detected by CCK-8 assay and colony-forming capability was evaluated using colony formation assays. Further, migration and invasion abilities were examined using wound-healing and transwell chamber assays, respectively. Cellular apoptosis after irradiation was assessed using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Results: HOXB2 was identified as a potential regulator of radioresistance in NPC. Our in vitro results indicate that HOXB2 overexpression (HOXB2-OE) promoted malignant behaviors including invasion, migration, proliferation, and inhibited the irradiation-induced apoptosis of NPC cells. Consistent with these results, HOXB2 knockdown (HOXB2-sh) exhibited the opposite trends in these biological activities. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEGs were enriched in the FOXO signaling pathway. Mechanistically, western blotting showed that HOXB2-OE inhibited forkhead box protein O1 (FOXO1) expression in NPC cells. Thereafter, we transferred the FOXO1-OE plasmid to HOXB2-OE NPC cells and found that overexpression of FOXO1 reversed cell proliferation, migration, invasion, and radioresistance profiles promoted by HOXB2 overexpression. Conclusion: Our findings showed that HOXB2 acts as a tumor promoter in NPC, activating malignant behaviors and radioresistance of tumors via FOXO1 regulation. Moreover, the inactivation of HOXB2 or activation of FOXO1 are potential strategies to inhibit tumor progression and overcome radioresistance in NPC.

HOXB-AS1 accelerates the tumorigenesis of glioblastoma via modulation of HOBX2 and HOBX3 at transcriptional and posttranscriptional levels.

Glioblastoma (GBM) is the most universal and invasive brain tumor among adults. Increasing studies have reported that long noncoding RNAs play vital roles in regulating downstream molecules at the transcriptional or posttranscriptional level in tumor progression. The purpose of the current research was to inquire the modulation mechanism by which homeobox B cluster antisense RNA 1 (HOXB-AS1) functioned in GBM. Our study first discovered the lifted expression of HOXB-AS1 and its nearby genes HOXB2 and HOXB3 in GBM and the positive relationship between HOXB-AS1 and HOXB2 or HOXB3. Loss-of-function assays and in vivo study detected that silencing of HOXB-AS1, HOXB2, or HOXB3 restrained the proliferation and induced the apoptosis in GBM. In addition, mechanism experiments demonstrated that HOXB-AS1 recruited interleukin enhancer-binding factor 3 (ILF3) to regulate HOXB2 and HOXB3 expression at the transcriptional level, and HOXB-AS1 sponged miR-186-5p to modulate HOXB2 and HOXB3 expression at posttranscriptional level. Finally, the regulatory mechanism of HOXB-AS1 in GBM was certified through rescue experiments. Our results indicated that HOXB-AS1 boost the HOXB2 or HOXB3 expression at the transcriptional and posttranscriptional levels. We detected the HOXB-AS1-ILF3-HOXB2/HOXB3 axis and HOXB-AS1-miR-186-5p-HOXB2/HOXB3 axis driving the GBM progression, which might generate more effective diagnostic biomarkers and therapeutic targets for patients with GBM.

Epigenetic induction of tumor stemness via the lipopolysaccharide-TET3-HOXB2 signaling axis in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell cancer (ESCC) is one kind of frequent digestive tumor. The inflammatory environment plays an important role in the tumorigenesis and development of ESCC. Cancer stem cells are a small group of tumor cells with stem cell characteristics, which can potentially hinder the tumor management and treatment. METHODS: ELISA was performed to detect the lipopolysaccharide concentration in cancer tissues. qPCR, Western blot, FACS, Immunohistochemistry, Immunofluorescence and Dot blot were applied to detect target genes expression. CCK-8, Colony-formation, Transwell, Sphere and Xenograft were conducted to investigate the function of cells, influenced by risk factors. The survival curve was drawn with the Kaplan-Meier product limit estimator. Nano-hmC-Seal-seq was utilized to detect the downstream target of TET3. ChIP-qPCR was adopted to demonstrate the transcriptional regulation of stem cell-associated genes by HOXB2. RESULTS: Lipopolysaccharide concentration was significantly up-regulated in ESCC. High concentration of lipopolysaccharide stimulation induced the stemness of ESCC cells. TET3 expression was elevated with lipopolysaccharide stimulation via p38/ERK-MAPK pathway in ESCC and negatively correlated with patients' survival. TET3 induced the stemness of ESCC cells. Nano-hmC-Seal-seq showed that TET3 overexpression led to a significant increase in 5hmC levels of HOXB2 gene region, which was thus identified as the downstream target of TET3. The binding of HOXB2 to NANOG and cMYC was verified by ChIP-qPCR. CONCLUSIONS: Lipopolysaccharide served as a tumor promotor in ESCC by inducing cancer cell stemness through the activation of a LPS-TET3-HOXB2 signaling axis, which might provide a novel therapeutic strategy for ESCC. Video Abstract.

HOXB2 and FOXC1 synergistically drive the progression of Wilms tumor.

OBJECTIVE: To uncover the expression patterns of HOXB2 and FOXC1 in Wilms tumor samples, and their synergistical regulations on the development of Wilms tumor. METHODS: Expression levels of HOXB2 and FOXC1 in 58 cases of Wilms tumor tissues and paracancerous ones were detected. The influences of HOXB2 and FOXC1 on prognosis in Wilms tumor patients were analyzed. Their regulatory effects on proliferative and migratory abilities in WT-CLS1 and HFWT cells were examined by cell counting kit-8 (CCK-8) and Transwell assay, respectively. The interaction between HOXB2 and FOXC1, and their synergistical regulation on the development of Wilms tumor were finally explored. RESULTS: HOXB2 and FOXC1 were upregulated in Wilms tumor tissues. Higher levels of HOXB2 and FOXC1 indicated higher risks of advanced stage and lymphatic metastasis, as well as worse prognosis in Wilms tumor patients. Knockdown of HOXB2 or FOXC1 weakened proliferative and migratory abilities in WT-CLS1 and HFWT cells, while the opposite trends were observed in those overexpressing HOXB2 or FOXC1. The positive interaction between HOXB2 and FOXC1 was identified, which synergistically drove the malignant development of Wilms tumor. CONCLUSIONS: HOXB2 and FOXC1 are upregulated in Wilms tumor samples, and they are closely linked to tumor staging and lymphatic metastasis in Wilms tumor patients. HOXB2 and FOXC1 synergistically drive the malignant development of Wilms tumor by stimulating proliferative and migratory potentials.

The role of HOXB2 and HOXB3 in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous aggressive disease and the most common form of adult leukemia. Mutations in the type III receptor tyrosine kinase FLT3 are found in more than 30% of AML patients. Drugs against FLT3 have been developed for the treatment of AML, but they lack specificity, show poor response and lead to the development of a resistant phenotype upon treatment. Therefore, a deeper understanding of FLT3 signaling will facilitate identification of additional pharmacological targets in FLT3-driven AML. In this report, we identify HOXB2 and HOXB3 as novel regulators of oncogenic FLT3-ITD-driven AML. We show that HOXB2 and HOXB3 expression is upregulated in a group of AML patients carrying FLT3-ITD. Overexpression of HOXB2 or HOXB3 in mouse pro-B cells resulted in decreased FLT3-ITD-dependent cell proliferation as well as colony formation and increased apoptosis. Expression of HOXB2 or HOXB3 resulted in a significant decrease in FLT3-ITD-induced AKT, ERK, p38 and STAT5 phosphorylation. Our data suggest that HOXB2 and HOXB3 act as tumor suppressors in FLT3-ITD driven AML.

HOXB2 promotes cisplatin resistance by upregulating lncRNA DANCR in ovarian cancer.

Ovarian cancer (OV) is a highly fatal malignant disease that commonly manifests at an advanced stage. Drug resistance, particularly platinum resistance, is a leading cause of treatment failure because first-line systemic chemotherapy primarily relies on platinum-based regimens. By analyzing the gene expression levels in the Cancer Genome Atlas database, Genotype-Tissue Expression database, and Gene Expression Omnibus datasets, we discerned that HOXB2 was highly expressed in OV and was associated with poor prognosis and cisplatin resistance. Immunohistochemistry and loss-of-function experiments on HOXB2 were conducted to explore its role in OV. We observed that suppressing HOXB2 could impair the growth and cisplatin resistance of OV in vivo and in vitro. Mechanical investigation and experimental validation based on RNA-Seq revealed that HOXB2 regulated ATP-binding cassette transporter members and the ERK signaling pathway. We further demonstrated that HOXB2 modulated the expression of long non-coding RNA DANCR, a differentiation antagonizing non-protein coding RNA, and thus influenced its downstream effectors ABCA1, ABCG1, and ERK signaling to boost drug resistance and cancer proliferation. These results verified that high expression of HOXB2 correlated with platinum resistance and poor prognosis of OV. Therefore, targeting HOXB2 may be a promising strategy for OV therapy.

The homeoprotein HOXB2 limits triple-negative breast carcinogenesis via extracellular matrix remodeling.

Homeobox genes and their encoded DNA-binding homeoproteins are master regulators of development. Consequently, these homeotic elements may regulate key steps in cancer pathogenesis. Here, using a combination of in silico analyses of large-scale patient datasets, in vitro RNAi phenotyping, and in vivo validation studies, we investigated the role of HOXB2 in different molecular subtypes of human breast cancer (BC). The gene expression signatures of HOXB2 are different across distinct BC subtypes due to various genetic alterations, but HOXB2 was specifically downregulated in the aggressive triple-negative subtype (TNBC). We found that the reduced expression of HOXB2 was correlated with the metastatic abilities (epithelial-to-mesenchymal transition) of TNBC cells. Further, we revealed that HOXB2 restrained TNBC aggressiveness by ECM organization. HOXB2 bound to the promoter regions of MATN3 and ECM2 and regulated their transcription levels. Forced expression of HOXB2 effectively prevented TNBC progression and metastasis in a mouse xenograft model. Reduction of HOXB2 and the HOXB2/MATN3/ECM2 transcriptional axis correlated with poor survival in patients with various cancers. Further, we found the long non-coding RNA HOXB-AS1 in complex with SMYD3, a lysine methyltransferase, as an epigenetic switch controlling HOXB2 expression. Overall, our results indicate a tumor-suppressive role of HOXB2 by maintaining ECM organization and delineate potential clinical utility of HOXB2 as a marker for TNBC patients.

Long noncoding RNA DLEU2 regulates the progression of Wilm's tumor via miR-539-3p/HOXB2 axis.

BACKGROUND: Wilm's tumor is the most common renal cancer in the pediatric age group. Long noncoding RNAs (lncRNAs) are a kind of RNA transcripts longer than ∼200 nucleotides, which have been revealed to be involved in the progression of Wilm's tumor. OBJECTIVE: The purpose of this study was to investigate the function and molecular mechanism of deleted in lymphocytic leukemia 2 (DLEU2) lncRNA in Wilm's tumor progression. STUDY DESIGN: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of DLEU2, miR-539-3p and HOXB2 mRNA in Wilm's tumor tissues and cells. Cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, colony formation assay, transwell assay, and flow cytometry were applied to explore the function of DLEU2 in Wilm's tumor cell malignant phenotypes and the regulatory mechanism among DLEU2, miR-539-3p and HOXB2 in Wilm's tumor cells. Western blot examined the protein levels of Bax, Bcl-2 and HOXB2. The relationship between miR-539-3p and DLEU2 or HOXB2 was verified by dual-luciferase reporter assay. Xenograft models of Wilm's tumor were established to study the role of DLEU2 in vivo. RESULTS: DLEU2 and HOXB2 were significantly highly expressed in primary Wilm's tumor tissues and in vitro cell lines. Silencing of DLEU2 reduced the proliferation, migration and invasion of Wilm's tumor cells, and promoted cell apoptosis. MiR-539-3p was confirmed to be a target of DLEU2. DLEU2 silencing inhibited the malignant behaviors of Wilm's tumor cells by releasing miR-539-3p. In addition, HOXB2 was a target of miR-539-3p. Overexpression of HOXB2 partially restored the inhibitory effects of miR-539-3p on Wilm's tumor cell malignant behaviors. Animal experiments also confirmed the anti-tumor effects of DLEU2 silencing in vivo. CONCLUSION: DLEU2 up-regulates the expression of HOXB2 by targetedly repressing miR-539-3p, thereby at least partially promoting the development of Wilm's tumor, these findings provided novel therapeutic targets for Wilm's tumor.

Transcriptome sequencing of facial adipose tissue reveals alterations in mRNAs of hemifacial microsomia.

Hemifacial microsomia (HFM) is a common congenital malformation of the craniofacial region, including mandibular hypoplasia, microtia, facial palsy and soft tissue deficiencies. However, it remains unclear which specific genes are involved in the pathogenesis of HFM. By identifying differentially expressed genes (DEGs) in deficient facial adipose tissue from HFM patients, we hope to provide a new insight into disease mechanisms from the transcriptome perspective. RNA sequencing (RNA-Seq) was performed with 10 facial adipose tissues from patients of HFM and healthy controls. Differentially expressed genes in HFM were validated by quantitative real-time PCR (qPCR). Functional annotations of the DEGs were analyzed with DESeq2 R package (1.20.0). A total of 1,244 genes were identified as DEGs between HFM patients and matched controls. Bioinformatic analysis predicted that the increased expression of HOXB2 and HAND2 were associated with facial deformity of HFM. Knockdown and overexpression of HOXB2 were achieved with lentiviral vectors. Cell proliferation, migration, and invasion assay was performed with adipose-derived stem cells (ADSC) to confirm the phenotype of HOXB2. We also found that PI3K-Akt signaling pathway and human papillomavirus infection were activated in HFM. In conclusion, we discovered potential genes, pathways and networks in HFM facial adipose tissue, which contributes to a better understanding of the pathogenesis of HFM.

Quercetin improves epithelial regeneration from airway basal cells of COPD patients.

Background: Airway basal cells from patients with chronic obstructive pulmonary disease (COPD) regenerate abnormal airway epithelium and this was associated with reduced expression of several genes involved in epithelial repair. Quercetin reduces goblet cell metaplasia and the expression of pro-inflammatory cytokines in COPD models. This study assessed whether quercetin improves epithelial regeneration from COPD airway basal cells. Methods: COPD airway basal cells were treated with DMSO or 1 µM quercetin for three days. The cells were then cultured at air/liquid interface (ALI) for up to 4 weeks. Basal cells from healthy donors cultured at air/liquid interface were used as controls. Polarization of cells was determined at 8 days of ALI. The cell types and IL-8 expression in differentiated cell cultures were quantified by flow cytometry and ELISA. Microarray analysis was conducted on DMSO or quercetin-treated COPD basal cells to identify differentially regulated genes (DEG) and the enriched biological pathways. Bronchial brushings from COPD patients treated with either placebo or quercetin for 6 months were used to confirm the effects of quercetin on gene expression. Results: Compared to DMSO, quercetin-treated COPD basal cells showed an increase in TER and regenerated the airway epithelium with more ciliated cells, and less goblet cells and IL-8. Comparison of DMSO- and quercetin-treated COPD basal cell transcriptomic profiles indicated that quercetin upregulated genes associated with tissue and epithelial development and differentiation. COPD patients treated with quercetin, but not placebo showed significantly increased expression of two developmental genes HOXB2 and ELF3, which were also increased in quercetin-treated COPD basal cells. Bronchial brushings from active smokers showed significantly increased mRNA expression of TGF-ß and IL-8, and it was reduced after quercetin treatment. Conclusions: These results indicate that quercetin may improve airway epithelial regeneration by increasing the expression of genes involved in epithelial development/differentiation in COPD. Trial registration: This study was registered at ClinicalTrials.gov on 6-18-2019. The study number is NCT03989271.

Temporal Expression of Hox Genes and Phox2b in the Rat Nucleus Ambiguus During Development: Implications on Laryngeal Innervation.

OBJECTIVES: Recurrent laryngeal nerve (RLN) injury results in synkinetic reinnervation and vocal fold paralysis. Investigation of cues expressed in the developing brainstem that influence correct selective targeting of intrinsic laryngeal muscles may elucidate post-injury abnormalities contributing to non-functional reinnervation. Primary targets of interest were Hoxb1 and Hoxb2, members of the Hox family that create overlapping gradients in the developing brain, and their target Phox2b, a transcription factor necessary for cranial nerve branchio- and visceromotoneuron survival. METHODS: Rat embryos at developmental days E14, E16, E18, and E20 (4 animals/age) were sectioned for RNA in situ hybridization to detect Hoxb1, Hoxb2, and Phox2b mRNA within the brainstem. Slides were costained with Islet1 antibody for identification of the nucleus ambiguus. Results were confirmed using immunohistochemistry. Sections were imaged on a confocal microscope. RNA and protein expressions were quantified using QuPath. Statistical analyses were performed using R. RESULTS: Hoxb1, Hoxb2, and Phox2b expressions varied according to embryologic age. Hoxb1 and Hoxb2 expression peaked at E16, with significant decreases at E18 and E20 (one-way ANOVA p = 0.001 for both). Phox2b expression was highest at E14 and trended downward with increased embryologic age (one-way ANOVA p = 0.005). CONCLUSION: Peak expression of Hoxb1 and Hoxb2 is observed at time points when the RLN arrives at the larynx and begins to branch toward individual muscles, positioning these gene products to be involved in cueing laryngeal motoneuron identity and target identification. Higher expression of Phox2b earlier in development suggests a role in laryngeal motoneuron formation. LEVEL OF EVIDENCE: NA Laryngoscope, 133:3462-3471, 2023.

Estrogen suppresses HOXB2 expression via ERα in breast cancer cells.

The expression of HOXB2, a homeobox transcription factor, is altered in a variety of solid tumors. Using an in vivo screen to identify regulators of breast tumor growth in murine mammary fat pads, Boimel and co-workers recently identified HOXB2 as a tumor suppressor. However, the mechanistic underpinnings of its role in breast cancer is not understood. Given the emerging interaction of estrogen-regulated gene expression and altered HOX gene expression network in the pathophysiology of breast cancer, this study addressed the relationship between estrogen signaling and HOXB2 expression. Using a mouse model and human breast cancer cell lines, we show that estrogen suppresses HOXB2 expression. Suppression of HOXB2 by PPT, a known ERα agonist, in MCF-7 and T47D cells indicated the involvement of ERα, which was confirmed by siRNA-mediated ERα knockdown experiments. In-silico analysis of the upstream promoter region revealed the presence of three putative EREs. Chromatin immunoprecipitation experiments showed that upon estrogen binding, ERα engaged with EREs in the 5' upstream region of HOXB2 in MCF-7 and T47D cells. Future investigations should address the implications of estrogen-mediated suppression on the proposed tumor suppressor function of HOXB2.

Genetic and Clinical Characterization of HOXB2 in Glioma.

BACKGROUND: Glioma is a highly aggressive and heterogeneous cancer with poor survival rates. Homeobox (HOX) genes are transcription factors that play pivotal roles in many aspects of cellular physiology, embryonic development, and tissue homeostasis. Mutations in HOX genes can lead to increased cancer predisposition. Abnormal expression of HOXB2 may result in the development and progression of tumors. However, its prognostic value and mechanism of dysregulation remain unclear. METHODS: The present study included 1001 glioma patients. The correlations between the expression of HOXB2 and subgroups of glioma were investigated by t-test analyses. The prognostic value of HOXB2 was explored by Kaplan-Meier analysis as well as univariate and multivariate Cox analyses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were employed to detect the biological function of HOXB2 in glioma. CCK-8 and transwell assays were performed to determine the role of HOXB2 in cell proliferation and invasion. RESULTS: HOXB2 was positively correlated with tumor grade and enriched in patients with isocitrate dehydrogenase 1 wild-type and age >41 years. HOXB2 was identified as an independent prognostic biomarker in glioma patients. HOXB2 was associated with cell invasion and promoted the proliferation of glioma cells in vitro. CONCLUSION: HOXB2 is an independent prognostic factor and contributes to tumor invasion in glioma patients.

miR-4324 functions as a tumor suppressor in colorectal cancer by targeting HOXB2.

OBJECTIVE: MicroRNAs (miRNAs) are reported to have crucial roles in human cancers; however, their role in colorectal cancer (CRC) remains largely unknown. METHODS: In this study, we analyzed the expression of miR-4324 in CRC cell lines using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We also examined miR-4324 expression in CRC tumor tissues using a miRNA expression dataset obtained from the Gene Expression Omnibus. We validated the connection between miR-4324 and homeobox B2 (HOXB2) using a luciferase activity reporter assay and western blotting. The effects of miR-4324 and HOXB2 on CRC cell malignant behaviors in vitro were further investigated. RESULTS: miR-4324 expression was significantly decreased in both CRC tumor tissues and cell lines. Overexpression of miR-4324 suppressed CRC cell proliferation, migration, and invasion. In contrast, overexpression of HOXB2 promoted CRC malignant cell behaviors. Furthermore, we validated HOXB2 as a direct target of miR-4324. CONCLUSIONS: miR-4324 expression was decreased in CRC. miR-4324 regulates CRC cell proliferation, migration, and invasion by targeting HOXB2.

LINC00662 promotes cell viability and metastasis in esophageal squamous cell carcinoma by sponging miR-340-5p and upregulating HOXB2.

BACKGROUND: Previous studies have shown that lncRNA LINC00662 plays an important role in pathogenesis of malignancies. The purpose of this study was to elucidate the regulatory mechanism of LINC00662 in esophageal squamous cell carcinoma (ESCC). METHODS: In this study, the regulatory mechanism of LINC00662 was investigated by RT-qPCR. MTT, transwell and dual luciferase reporter assays. RESULTS: Upregulation of LINC00662 was found in ESCC and associated with worse clinical outcomes in ESCC patients. More importantly, knockdown of LINC00662 restrained cell proliferation, migration and invasion in ESCC. In addition, LINC00662 acts as a molecular sponge for miR-340-5p in ESCC, and miR-340-5p directly targets HOXB2. HOXB2 expression can be positively regulated by LINC00662 in ESCC. Furthermore, HOXB2 downregulation or miR-340-5p overexpression weakened the carcinogenesis of LINC00662 in ESCC. CONCLUSIONS: LncRNA LINC00662 promotes the progression of ESCC by upregulating HOXB2 by sponging miR-340-5p.

LncRNA RGMB-AS1 Promotes Glioma Growth and Invasion Through miR-1200/HOXB2 Axis.

BACKGROUND: Dysfunction of long noncoding RNA (lncRNA) is associated with tumorigenesis of various malignancies, including glioma. LncRNA RGMB-AS1 (RGMB antisense RNA 1) has been reported to participate in initiation and progression of several cancers, such as lung cancer, hepatocellular carcinoma and laryngeal squamous cell carcinoma. Nevertheless, whether RGMB-AS1 regulates glioma development is not investigated. In this study, we aimed to determine its roles in glioma. METHODS: qRT-PCR and Western blotting were used to measure gene expression. CCK8 and colony formation assays were utilized to analyze proliferation. Transwell assay was used to determine cell migration and invasion. Luciferase reporter assay was used to validate the interactions among RGMB-AS1, miR-1200 and HOXB2. RESULTS: RGMB-AS1 was upregulated in glioma tissues and associated with glioma grade and patients' prognosis. Moreover, RGMB-AS1 silencing significantly inhibited the proliferation, migration and invasion of glioma cells. RGMB-AS1 downregulation led to more tumor cells arrested in the quiescent state. Mechanistically, we found that RGMB-AS1 was a molecular sponge for miR-1200. MiR-1200 level was inhibited by RGMB-AS1. And RGMB-AS1 promoted HOXB2 expression via sponging miR-1200. Restoration of HOXB2 effectively rescued the abilities of proliferation, migration and invasion in RGMB-AS1-depleted glioma cells. CONCLUSION: Collectively, our work clarified that RGMB-AS1/miR-1200/HOXB2 signaling exerts an essential role in regulating glioma progression.

HOXB2 is a Putative Tumour Promotor in Human Bladder Cancer.

BACKGROUND/AIM: The present study aimed to investigate the role of Homebox B2 (HOXB2) in bladder cancer (BC). MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA) dataset was used to analyse HOXB2 expression in BC. The influence of HOXB2 on the cellular functions of BC cells was determined in both HOXB2 knockdown and HOXB2 overexpressed BC cell lines using in vitro assays. RESULTS: HOXB2 mRNA was significantly upregulated in luminal infiltrated and luminal papillary subtypes of BC. Drug Metabolism Cytochrome P450 was significantly enriched in BCs expressing high levels of HOXB2. Knockdown of HOXB2 from EJ138 cells reduced growth, adhesion and invasion. In contrast, overexpression of HOXB2 in RT112 cells induced growth and adhesion of bladder cancer cells. CONCLUSION: Increased HOXB2 expression in papillary BC can promote cell growth and adhesion of BC cells. Drug Metabolism Cytochrome P450 pathway was enriched in BCs overexpressing HOXB2.