BACKGROUND: Endometrial cancer (EC) is the sixth most frequent cancer in women worldwide and has higher fatality rates. The pathophysiology of EC is complex, and there are currently no reliable methods for diagnosing and treating the condition. Long non-coding RNA (lncRNA), according to mounting evidence, is vital to the pathophysiology of EC. HOTAIR is regarded as a significant prognostic indicator of EC. ZBTB7A decreased EC proliferation and migration, according to recent studies, however the underlying mechanism still needs to be clarified.
METHODS: The research utilized RT-qPCR to measure HOTAIR expression in clinical EC tissues and various EC cell lines. Kaplan-Meier survival analysis was employed to correlate HOTAIR levels with patient prognosis. Additionally, the study examined the interaction between ZBTB7A and HOTAIR using bioinformatics tools and ChIP assays. The experimental approach also involved manipulating the expression levels of HOTAIR and ZBTB7A in EC cell lines and assessing the impact on various cellular processes and gene expression.
RESULTS: The study found significantly higher levels of HOTAIR in EC tissues compared to adjacent normal tissues, with high HOTAIR expression correlating with poorer survival rates and advanced cancer characteristics. EC cell lines like HEC-1 A and KLE showed higher HOTAIR levels compared to normal cells. Knockdown of HOTAIR in these cell lines reduced proliferation, angiogenesis, and migration. ZBTB7A was found to be inversely correlated with HOTAIR, and its overexpression led to a decrease in HOTAIR levels and a reduction in malignant cell behaviors. The study also uncovered that HOTAIR interacts with ELAVL1 to regulate SOX17, which in turn activates the Wnt/β-catenin pathway, promoting malignant behaviors in EC cells.
CONCLUSIONS: HOTAIR is a critical regulator in EC, contributing to tumor growth and poor prognosis. Its interaction with ZBTB7A and regulation of SOX17 via the Wnt/β-catenin pathway underlines its potential as a therapeutic target.

BACKGROUND: The importance of long noncoding RNAs (lncRNAs) in various biological processes has been increasingly recognized in recent years. This study investigated how gene polymorphism in HOX transcript antisense RNA (HOTAIR) lncRNA affects the predisposition to chronic kidney disease (CKD).
METHODS: This study comprised 150 patients with CKD and 150 healthy controls. A PCR-RFLP and ARMS-PCR techniques were used for genotyping the five target polymorphisms.
RESULTS: According to our findings, rs4759314 confers strong protection against CKD in allelic, dominant, and codominant heterozygote genetic patterns. Furthermore, rs3816153 decreased CKD risk by 78% when TT versus GG, 55% when GG+GT versus TT, and 74% when GT versus TT+GG. In contrast, the CC+CT genotype [odds ratio (OR) = 1.66, 95% confidence intervals (CIs) = 1.05-2.63] and the T allele (OR = 1.50, 95% CI = 1.06-2.11) of rs12826786, as well as the TT genotype (OR = 2.52, 95% CI = 1.06-5.98) of rs3816153 markedly increased the risk of CKD in the Iranian population. Although no linkage disequilibrium was found between the studied variants, the Crs12826786Trs920778Grs1899663Grs4759314Grs3816153 haplotype was associated with a decreased risk of CKD by 86% (OR = 0.14, 95% CI = 0.03-0.66).
CONCLUSIONS: The rs920778 was not correlated with CKD risk, whereas the HOTAIR rs4759314, rs12826786, rs1899663, and rs3816153 polymorphisms affected the risk of CKD in our population. It seems essential to conduct repeated studies across various ethnic groups to explore the link between HOTAIR variants and their impact on the disease outcome.

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

Metastasis is the hallmark of cancer that is responsible for the greatest number of cancer-related deaths. As a critical regulator of the Hippo pathway, the phosphorylation status of Yes-associated protein 1 (YAP1), mainly at S127, is critical for its oncogenic function. Herein, we aim to investigate the precise molecular mechanism between long noncoding RNA HOX transcript antisense RNA (HOTAIR) and YAP1 phosphorylation in regulating tumor migration and invasion. In this study, we showed that inhibition of HOTAIR significantly decreased the migration and invasion of cancer cells both in vitro and in vivo through elevating the phosphorylation level of YAP1 on serine 127, demonstrating a tumor suppressive role of YAP1 S127 phosphorylation. Through bisulfite sequencing PCR (BSP), we found that inhibition of HOTAIR dramatically increased Large Tumor Suppressor Kinase 1 (LATS1) expression by regulating LATS1 methylation via DNA methyltransferase 3β (DNMT3B). In accordance with this observation, DNMT3B just only altered the distribution of YAP1 in the cytoplasm and the nucleus by inhibiting its phosphorylation, but did not change its total expression. Mechanistically, we discovered that HOTAIR suppressed YAP1 S127 phosphorylation by regulating the methylation of LATS1 via DNMT3B, the consequence of which is the translocation of YAP1 into the nucleus, reinforcing its coactivating transcriptional function, which in turn promotes the migration and invasion of cancer cells. Collectively, our data reveal that the phosphorylation of YAP1 S127 plays a vital role in the function of HOTAIR in tumorigenicity, and should be taken into consideration in future therapeutic strategies for cervical cancer.

BACKGROUND: Papillary thyroid carcinoma (PTC) is one of the most common subtypes of thyroid carcinoma. Exosomal miR-181a plays an important role in the development of PTC. This study examined the regulatory mechanism of miR-181a under conditions of hypoxia and its impact on angiogenesis.
METHODS: A ribonucleoprotein immunoprecipitation (RIP) experiment was conducted to verify the interaction between HOTAIR and RELA. The relationship between RELA and the miR-181a promoter was detected by ChIP-qPCR. Short hairpin (sh) RNA was designed to knock down HOTAIR in TPC cells. The underlying mechanism of miR-181a was verified by use of dual-luciferase assays and rescue experiments. The regulatory effect of GATA6 on angiogenesis was studied using CCK8, EdU, Transwell, and western blot assays.
RESULTS: A RIP assay showed that HOTAIR could bind to RELA under hypoxic conditions. ChIP-qPCR and dual luciferase assays showed RELA could interact with the miR181a promoter and upregulate miR-181a. Knockdown of HOTAIR downregulated miR-181a in TPC-1 cells, and the downregulation could be rescued by RELA overexpression. MiR-181a downregulated GATA6 in HUVEC cells. Overexpression of GATA6 inhibited HUVEC proliferation, migration, tube formation, and EGFR expression. Exosomal miR-181a promoted angiogenesis by downregulating GATA6 expression.
CONCLUSIONS: HOTAIR activated RELA to upregulate miR-181a during hypoxia. Exosomal miR-181a promotes tumor angiogenesis by downregulating GATA6.

Laryngeal squamous cell carcinoma (LSCC) is a significant global health burden, for which there has been limited evidence of improved survival rates. Although the roles of hypoxia-inducible factor (HIF)1α and HIF2α have been well documented in hypoxia, the involvement of HIF3α, particularly in LSCC, has been inadequately explored. The present study aimed to investigate the correlation between HIFα subunits and the hypoxia-related long noncoding RNAs (lncRNAs) MALAT1 and HOTAIR in 63 patients diagnosed with LSCC. Total RNA was extracted from fresh-frozen laryngeal tumor and adjacent normal tissues, and was subjected to reverse transcription-quantitative PCR for target detection. Statistical analyses were conducted using SPSS software, with significance set at P<0.05. The present study is the first, to the best of our knowledge, to report a positive moderate monotonic correlation (rs=0.347) and moderately strong positive linear correlation (r=0.630) between HIF3α mRNA and lncRNA MALAT1 in LSCC. Regression analysis revealed a direct association between 39.6% of both variables. Additionally, a positive correlation was observed between lncRNAs MALAT1 and HOTAIR (rs=0.353); HIF2α mRNA and lncRNA MALAT1 (rs=0.431); HIF3α mRNA and lncRNA HOTAIR (rs=0.279); and HIF3α mRNA and HIF2α mRNA (rs=0.285). Notably, a significant negative correlation (rs=-0.341) was detected between HIF3α mRNA and HIF1α mRNA, potentially indicative of the HIF switch or negative regulation. In addition, the present study investigated the association between HIFα subunits and the clinicopathological characteristics of patients. The results revealed a notable association between HIF1α transcript levels and the location of LSCC; specifically, subglottic tumors exhibited elevated HIF1α levels compared with glottic and supraglottic LSCC. Furthermore, a significant association was identified between HIF3α transcript levels and patient age (P=0.032) and positive family history (P=0.047). In conclusion, the present findings suggested a pivotal role for HIF3α in LSCC development, potentially involving direct regulation of lncRNA MALAT1. However, further research is warranted to elucidate its precise mechanisms.

Long non-coding RNAs (lncRNAs) are involved significantly in the development of human cancers. lncRNA HOTAIR has been reported to play an oncogenic role in many human cancers. Its specific regulatory role is still elusive. And it might have enormous potential to interpret the malignant progression of tumors in a broader perspective, that is, in pan-cancer. We comprehensively investigated the effect of HOTAIR expression on tumor prognosis across human malignancies by analyzing multiple cancer-related databases like The Cancer Genome Atlas (TCGA) and Tumor Immune Estimation Resource (TIMER). Bioinformatics data indicated that HOTAIR was overexpressed in most of these human malignancies and was significantly associated with the prognosis of patients with cancer, especially in colorectal cancer (CRC). Subsequently, this study further clarified the utility of HOTAIR that downregulation of its expression could result in reduced proliferation and invasion of CRC cells. Mechanistically, HOTAIR upregulated the metabolic enzymes UPP1 by recruiting histone methyltransferase EZH2, thereby increasing the tumor progression. Our results highlight the essential role of HOTAIR in pan-cancer and uridine bypass, suggesting that the HOTAIR/EZH2/UPP1 axis might be a novel target for overcoming CRC. We anticipate that the role of HOTAIR in metabolism could be important in the context of CRC and even exploited for therapeutic purposes.

BACKGROUND: Breast cancer is the most frequent cancer among women worldwide with significant disproportionate mortality rates in developing countries. Although clinical management of breast cancer has been immensely improved, refinement in the prognostic and recurrent markers is still needed. Long non-coding RNAs (lncRNA) HOTAIR has recently been associated with poor outcome and is potentially used as a prognostic marker in breast cancer.
METHODS: We comprehensively reviewed studies evaluating lncRNA HOTAIR in association with overall and disease-free survivals in breast cancers. Systematic searches were performed in Pubmed, ProQuest, ScienceDirect, Scopus, Google Scholar, Semantic Scholar, Springer, Nature, Sage Journals, and Wiley databases using combination keywords \"long non-coding RNA,\" \"lncRNA,\" \"HOX transcript antisense RNA,\" \"HOTAIR,\" \"breast can-cer,\" \"carcinoma mammae,\" \"prognosis,\" and \"survival.\" Risk of bias score was used to assess quality of studies, I2 test was conducted to assess heterogeneity. Meta-analysis was performed to compare HOTAIR expression with breast cancer survival rates using STATA v.17 software.
RESULTS: Of the total 1,504 screened studies, seven studies were included in the meta-analysis involving 533 patients. High expression of HOTAIR was associated with poor survival rates (pooled HR: 1.69; 95%CI: 1.11-2.59; p=0.015), shorter overall survival (OS) (pooled HR: 1.33; 95%CI: 0.78-2.26; p=0.455), poor disease-free survival (DFS) (pooled HR: 2.40; 95%CI: 1.63-3.53; p<0.001), poor distant metastatic-free survival (MFS) (HR: 1.75; 95%CI: 1.13-2.71; p=0.012). In addition, overexpression of HOTAIR was associated with positive lymph node infiltration (pooled OR: 2.38; 95%CI: 0.53-10.69; p=0.26) and ductal type cancer (pooled OR: 3.27; 95%CI: 1.15-9.30; p=0.03).
CONCLUSIONS: Upregulation of lncRNA HOTAIR is associated with worse DFS aand MFS that can potentially be used as a prognostic marker in breast cancer patients.

UNASSIGNED: Recent studies have implicated dysregulated long non-coding RNA (lncRNA) levels in the pathogenesis of type 2 diabetes (T2D). This study aimed to assess the expression of circulating HOTAIR and uc.48+, examining their correlation with clinical and biochemical variables in T2D patients, pre-diabetic individuals, and healthy controls.
UNASSIGNED: Peripheral blood levels of lncRNAs were quantified using QRT-PCR in 65 T2D patients, 63 pre-diabetic individuals, and 63 healthy subjects. Pathway enrichment analysis was conducted to explore the functional enrichment of lncRNA-miRNA targets.
UNASSIGNED: Analysis revealed a significantly elevated circulating level of HOTAIR in both T2D (P < 0.0001) and pre-diabetic patients (P = 0.04) compared to controls. ROC analysis demonstrated that, at a cutoff value of 9.1, with a sensitivity of 80% and specificity of 62%, HOTAIR could distinguish T2D patients from controls (AUC = 0.723, 95% CI 0.637-0.799, P < 0.0001). Spearman correlation analysis identified a significant positive correlation between HOTAIR expression, HbA1c, and insulin resistance (P < 0.005). MiRNA enrichment analysis indicated significant enrichment of diabetes-related pathways among HOTAIR\'s miRNA targets. Conversely, no significant difference in uc.48+ circulating levels between groups was observed, but a significant positive correlation emerged between uc.48+ and systolic blood pressure.
UNASSIGNED: This study provides evidence that elevated HOTAIR expression levels are associated with T2D progression, suggesting their potential as biomarkers for early diagnosis and prognosis.

UNASSIGNED: Previous studies have revealed dexmedetomidine have potential protective effects on vital organs by inhibiting the release of inflammatory cytokines. To investigate the effects of dexmedetomidine on sepsis, especially in the initial inflammatory stage of sepsis. RAW264.7 cells were used as the cell model in this study to elucidate the underlying mechanisms.
UNASSIGNED: In this study, we conducted several assays to investigate the mechanisms of dexmedetomidine and HOTAIR in sepsis. Cell viability was assessed using the CCK-8 kit, while inflammation responses were measured using ELISA for IL-1β, IL-6, and TNF-α. Additionally, we employed qPCR, MeRIP, and RIP to further explore the underlying mechanisms.
UNASSIGNED: Our findings indicate that dexmedetomidine treatment enhanced cell viability and reduced the production of inflammatory cytokines in LPS-treated RAW264.7 cells. Furthermore, we observed that the expression of HOTAIR was increased in LPS-treated RAW264.7 cells, which was then decreased upon dexmedetomidine pre-treatment. Further investigation demonstrated that HOTAIR could counteract the beneficial effects of dexmedetomidine on cell viability and cytokine production. Interestingly, we discovered that YTHDF1 targeted HOTAIR and was upregulated in LPS-treated RAW264.7 cells, but reduced in dexmedetomidine treatment. We also found that YTHDF1 increased HOTAIR and HOTAIR m6A levels.
UNASSIGNED: Collectively, our results suggest that dexmedetomidine downregulates HOTAIR and YTHDF1 expression, which in turn inhibits the biological behavior of LPS-treated RAW264.7 cells. This finding has potential implications for the prevention and treatment of sepsis-induced kidney injury.