lncRNA HOTAIR Research Articles

Single-Cell Multiplexed Signal Amplification Strategy Based on Catalytic Hairpin Self-Assembly and CRISPR/Cas12a for Exploring the Relationship between lncRNA HOTAIR and miRNA-122 in Individual Hepatocytes.

The long noncoding RNA (lncRNA) HOTAIR has been shown to act as an oncogene in a variety of cancers, including hepatocellular carcinoma (HCC). MicroRNA-122 (miR-122) is a key liver-specific miRNA that is frequently inhibited in HCC and is associated with poor prognosis. However, a potential relationship between HOTAIR and miR-122 in individual hepatocytes has not been explored. To this end, we propose here an intracellular catalytic hairpin self-assembly-CRISPR/Cas12a tandem multiplexed signal amplification strategy for the simultaneous quantification of HOTAIR and miRNA-122 in a single hepatocyte. We applied this method to analyze both normal HL-7702 liver cells and HepG2 HCC cells, and found that HL-7702 cells contained large amounts of miRNA-122, while the content of miRNA-122 in HepG2 cells was low. However, the level of HOTAIR in HepG2 cells was much higher than that in HL-7702 cells, confirming the overexpression of HOTAIR in HCC cells. We achieved the simultaneous absolute quantification of HOTAIR and miRNA-122 in single cells, providing an important method to study the relationships between these two RNA molecules in individual cells.

Detection and validity of long non-coding RNAs HOST2, HOTAIR, HOXA-AS2, and MALAT1 as biomarkers for hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is one of the most common cancers in the world. Long noncoding RNAs (lncRNAs) could contribute significantly to HCC development through diverse mechanisms, such as the recruitment of many regulatory protein complexes. This study aimed to evaluate the expression levels of the lncRNAs HOST2, HOTAIR, HOXA-AS2, and MALAT1 in liver cirrhosis and HCC and also assess their diagnostic performance as biomarkers for HCC. MethodsIn total, 180 participants were in this study, classified into three groups (60 participants in each): Group I (hepatocellular carcinoma patients), Group II (liver cirrhosis patients), and Group III (apparently healthy individuals). The expressions of the HOST2, HOTAIR, HOXA-AS2, and MALAT1 lncRNAs were detected using a reverse-transcriptase real-time polymerase chain reaction (qRT-PCR). ResultsThe expression levels of HOST2, HOTAIR, HOXA-AS2, and MALAT1 lncRNAs were markedly increased in the HCC patients compared with those in the cirrhotic patients and controls. They also exhibited greater sensitivity as diagnostic biomarkers than alpha-fetoprotein. ConclusionsThe HOTAIR, HOST2, HOXA-AS2, and MALAT1 lncRNAs exhibit promising potential as valuable diagnostic biomarkers of HCC and in differentiating HCC from liver cirrhosis. Furthermore, combining alpha-fetoprotein can yield higher accuracy.

Neuroprotective effect of empagliflozin against doxorubicin-induced chemobrain in rats: Interplay between SIRT-1/MuRF-1/PARP-1/NLRP3 signaling pathways and enhanced expression of miRNA-34a and LncRNA HOTAIR

Chemobrain, a challenging side effect of doxorubicin (DOX)-based chemotherapy, impairs cognitive abilities in cancer survivors. DOX triggers chemobrain via oxidative stress, leading to inflammation and apoptosis. Empagliflozin (EMPA), a sodium glucose co-transporter-2 inhibitor, demonstrated neuroprotective effects by reducing reactive oxygen species (ROS) and inflammation, but its protective mechanisms against DOX-induced chemobrain is not fully known. Thus, this study aimed to investigate EMPA’s neuroprotective effects on DOX-induced chemobrain in rats and to uncover the underlying protective mechanisms. Fifty male Wistar rats were divided into control, EMPA, DOX (2 mg/kg, IP, once/week for 4 weeks), and two treated groups (DOX+ EMPA 5 and 10 mg/kg/day, PO, for 4 weeks). Behavioral tests showed improved memory, motor performance, and reduced anxiety in EMPA-treated groups compared to DOX, with superior results at the higher dose. Histopathological analysis revealed increased intact neurons in the cortex and hippocampus in EMPA-treated groups, with 346.4 % increase in CA3 (p < 0.0001), 19.1 % in dentate gyrus (p = 0.0006), and 362.6 % in cortex (p < 0.0001) in the high-dose EMPA group. Biochemical investigations of the high-dose EMPA group revealed significant decreases in inflammatory and apoptotic markers (JNK/PARP-1/NLRP3/MuRF-1/FOXO-1), increased SIRT-1 protein expression by 389.9 % (p < 0.0001), and reduced miRNA-34a and LncRNA HOTAIR gene expression (50.4 % and 53.4 % respectively, p < 0.0001) relative to DOX group. Conclusively, EMPA demonstrated superior behavioral and histopathological outcomes particularly at higher dose, positioning it as a promising neuroprotective candidate against DOX-induced chemobrain, possibly through modulating SIRT-1, NF-κb, NLRP3, and oxidative stress pathways.

Retraction Note: LncRNA HOTAIR regulates HIF-1α/AXL signaling through inhibition of miR-217 in renal cell carcinoma

Retraction Note: LncRNA HOTAIR regulates HIF-1α/AXL signaling through inhibition of miR-217 in renal cell carcinoma

Retracted] LncRNA HOTAIR controls the expression of Rab22a by sponging miR‑373 in ovarian cancer.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the cell apoptotic data shown in Fig. 3C and the Hoeschst 33342‑stained images in Fig. 3D on p. 2468, and certain of the scratch‑wound assay data shown in Fig. 5E on p. 2470 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Molecular Medicine Reports, or were submitted for publication at around the same time. Owing to the fact that some of the abovementioned data had already apparently been published previously, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 14: 2465‑2472, 2016; DOI: 10.3892/mmr.2016.5572].

LncRNA HOTAIR and Cardiovascular diseases.

Cardiovascular diseases (CVDs) a major contributor to global mortality rates, with a steadily rising prevalence observed across the world. Understanding the molecular mechanisms that underlie the signaling pathways implicated in the pathogenesis of CVDs represents a salient and advantageous avenue toward the development of precision and targeted therapeutics. A recent development in CVDs research is the discovery of long non-coding RNAs (lncRNAs), which are now understood to have crucial roles in the onset and development of several pathophysiological processes. The distinct expression patterns exhibited by lncRNAs in various CVDs contexts, present a significant opportunity for their utilization as both biomarkers and targets for therapeutic intervention. Among the various identified lncRNAs, HOX antisense intergenic RNA (HOTAIR) functions as signaling molecules that are significantly implicated in the pathogenesis of cardiovascular disorders in response to risk factors. HOTAIR has been observed to circulate within the bloodstream and possesses an integral epigenetic regulatory function in the transcriptional pathways of many diseases. Recent studies have suggested that HOTAIR offers promise as a biomarker for the detection and treatment of CVDs. The investigation on HOTAIR's role in CVDs, however, is still in its early phases. The goal of the current study is to give a thorough overview of recent developments in the field of analyzing the molecular mechanism of HOTAIR in controlling the pathophysiological processes of CVDs as well as its possible therapeutic uses.

Engineering artificial non-coding RNAs for targeted protein degradation.

Targeted protein degradation has become a notable drug development strategy, but its application has been limited by the dependence on protein-based chimeras with restricted genetic manipulation capabilities. The use of long non-coding RNAs (lncRNAs) has emerged as a viable alternative, offering interactions with cellular proteins to modulate pathways and enhance degradation capabilities. Here we introduce a strategy employing artificial lncRNAs (alncRNAs) for precise targeted protein degradation. By integrating RNA aptamers and sequences from the lncRNA HOTAIR, our alncRNAs specifically target and facilitate the ubiquitination and degradation of oncogenic transcription factors and tumor-related proteins, such as c-MYC, NF-κB, ETS-1, KRAS and EGFR. These alncRNAs show potential in reducing malignant phenotypes in cells, both in vitro and in vivo, offering advantages in efficiency, adaptability and versatility. This research enhances knowledge of lncRNA-driven protein degradation and presents an effective method for targeted therapies.

CRISPR-Enhanced Photocurrent Polarity Switching for Dual-lncRNA Detection Combining Deep Learning for Cancer Diagnosis.

Abnormal expression in long noncoding RNAs (lncRNAs) is closely associated with cancers. Herein, a novel CRISPR/Cas13a-enhanced photocurrent-polarity-switching photoelectrochemical (PEC) biosensor was engineered for the joint detection of dual lncRNAs, using deep learning (DL) to assist in cancer diagnosis. After target lncRNA-activated CRISPR/Cas13a cleaves to induce DNAzyme bidirectional walkers with the help of cofactor Mg2+, nitrogen-doped carbon-Cu/Cu2O octahedra are introduced into the biosensor, producing a photocurrent in the opposite direction of CdS quantum dots (QDs). The developed PEC biosensor shows high specificity and sensitivity with limits of detection down to 25.5 aM for lncRNA HOTAIR and 53.1 aM for lncRNA MALAT1. More importantly, this platform for the lncRNA joint assay in whole blood can successfully differentiate cancers from healthy people. Furthermore, the DL model is applied to explore the potential pattern hidden in data of the established technology, and the accuracy of DL cancer diagnosis can acquire 93.3%. Consequently, the developed platform offers a new avenue for lncRNA joint detection and early intelligent diagnosis of cancer.

Natural products and long noncoding RNA signatures in gallbladder cancer: a review focuses on pathogenesis, diagnosis, and drug resistance.

Gallbladder cancer (GBC) is an aggressive and lethal malignancy with a poor prognosis. Long noncoding RNAs (lncRNAs) and natural products have emerged as key orchestrators of cancer pathogenesis through widespread dysregulation across GBC transcriptomes. Functional studies have revealed that lncRNAs interact with oncoproteins and tumor suppressors to control proliferation, invasion, metastasis, angiogenesis, stemness, and drug resistance. Curcumin, baicalein, oleanolic acid, shikonin, oxymatrine, arctigenin, liensinine, fangchinoline, and dioscin are a few examples of natural compounds that have demonstrated promising anticancer activities against GBC through the regulation of important signaling pathways. The lncRNAs, i.e., SNHG6, Linc00261, GALM, OIP5-AS1, FOXD2-AS1, MINCR, DGCR5, MEG3, GATA6-AS, TUG1, and DILC, are key players in regulating the aforementioned processes. For example, the lncRNAs FOXD2-AS1, DILC, and HOTAIR activate oncogenes such as DNMT1, Wnt/β-catenin, BMI1, and c-Myc, whereas MEG3 and GATA6-AS suppress the tumor proteins NF-κB, EZH2, and miR-421. Clinically, specific lncRNAs can serve as diagnostic or prognostic biomarkers based on overexpression correlating with advanced TNM stage, metastasis, chemoresistance, and poor survival. Therapeutically, targeting aberrant lncRNAs with siRNA or antisense oligos disrupts their oncogenic signaling and inhibits GBC progression. Overall, dysfunctional lncRNA regulatory circuits offer multiple avenues for precision medicine approaches to improve early GBC detection and overcome this deadly cancer. They have the potential to serve as novel biomarkers as they are detectable in bodily fluids and tissues. These findings enhance gallbladder treatments, mitigating resistance to chemo- and radiotherapy.

Deciphering the Temporal-Spatial Interactive Heterogeneity of Long Non-Coding RNAs and RNA-Binding Proteins in Living Cells at Single-Cell Resolution.

The investigation of long noncoding RNAs (lncRNAs) and RNA binding proteins (RBPs) interactions in living cell holds great significance for elucidating their critical roles in a variety of biological activities, but limited techniques are available to profile the temporal-spatial dynamic heterogeneity. Here, we introduced a molecular beacon-functionalized nanoneedle array designed for spatially resolved profiling of lncRNA-RBP interactions (Nano-SpatiaLR). A nanoneedle array modified with a molecular beacon is employed to selectively isolate specific intracellular lncRNAs and their associated RBPs without affecting cell viability. The RBPs are then in situ analyzed with a fluorescent labeled antibody and colocalized with lncRNA signals to get a quantitative measurement of their dynamic interactions. Additionally, leveraging the spatial distribution and nanoscale modality of the nanoneedle array, this technique provides the spatial heterogeneity information on cellular lncRNA-RBPs interaction at single cell resolution. In this study, we tracked the temporal-spatial interactive heterogeneity dynamics of lncRNA-RBPs interaction within living cells across different biological progresses. Our findings demonstrated that the interactions between lncRNA HOTAIR and RBPs EZH2 and LSD1 undergo significant changes in response to drug treatments, particularly in tumor cells. Moreover, these interactions become more intensified as tumor cells aggregate during the proliferation process.

Development of a DNAzyme-Driven Fluorescent Light-Up Aptasensor for Label-Free Detection of Multiple lncRNAs.

Long noncoding RNAs (lncRNAs) act as the dynamic regulatory molecules that control the expression of genes and affect numerous biological processes, and their dysregulation is associated with tumor progression. Herein, we develop a fluorescent light-up aptasensor to simultaneously measure multiple lncRNAs in living cells and breast tissue samples based on the DNAzyme-mediated cleavage reaction and transcription-driven synthesis of light-up aptamers. When target lncRNAs are present, they can be recognized by template probes to form the active DNAzyme structures, initiating the T4 PNK-catalyzed dephosphorylation-triggered extension reaction to generate double-strand DNAs with the T7 promoter sequences. The corresponding T7 promoters can initiate the transcription amplification catalyzed by the T7 RNA polymerase to generate abundant Broccoli aptamers and malachite green aptamers, which can bind DFHBI-1T and MG to generate strong fluorescence signals. Taking advantage of the good selectivity of DNAzyme-mediated cleavage of lncRNAs, high amplification efficiency of T7 transcription-driven amplification reaction, and bright fluorescence of the RNA aptamer-fluorophore complex, this method exhibits high sensitivity with a detection limit of 21.4 aM for lncRNA HOTAIR and 18.47 aM for lncRNA MALAT1, and it can accurately measure multiple lncRNAs in both tumor cell lines and breast tissue samples, providing a powerful paradigm for biomedical research and early clinic diagnostics.

METTL14-mediated upregulation of lncRNA HOTAIR represses PP1α expression by promoting H3K4me1 demethylation in oxycodone-treated mice.

N6-methyladenosine (m6A) methylation is a vital epigenetic mechanism associated with drug addiction. However, the relationship between m6A modification and oxycodone rewarding is less well explored. Based on an open field test, the present study evaluated oxycodone rewarding using chromatin immunoprecipitation PCR, immunofluorescence, and RNA sequencing. A marked increase in METTL14 protein and a decrease in PP1α protein due to oxycodone abundance in the striatal neurons were observed in a dose- and time-dependent manner. Oxycodone markedly increased LSD1 expression, and decreased H3K4me1 expression in the striatum. In the open field test, intra-striatal injection of METTL14 siRNA, HOTAIR siRNA, or LSD1 shRNA blocked oxycodone-induced increase in locomotor activity. The downregulation of PP1α was also inhibited after treatment with METTL14/HOTAIR siRNA and LSD1 shRNA. Enhanced binding of LSD1 with CoRest and of CoRest with the PP1α gene induced by oxycodone was also reversed by LSD1 shRNA. In addition, H3K4me1 demethylation was also blocked by the treatment. In summary, the investigation confirmed that METTL14-mediated upregulation of HOTAIR resulted in the repression of PP1α, which in turn facilitated the recruitment of LSD1, thus catalyzing H3K4me1 demethylation and promoting oxycodone addiction.

Circulating lncRNAs HOTTIP and HOTAIR as Potential Biomarkers in Crigler-Najjar Syndrome: A Preliminary Report from Shiraz Liver Transplant Research Center

Crigler-Najjar syndrome (CNS) is a rare autosomal recessive disorder characterized by impaired bilirubin metabolism, leading to neurotoxic unconjugated bilirubin accumulation. Liver transplantation remains the only effective treatment, highlighting the need for novel diagnostic and therapeutic approaches. Long non-coding RNAs (lncRNAs) have emerged as potential biomarkers in various diseases, including cancer. This study aimed to evaluate the expression of lncRNAs HOTTIP and HOTAIR in CNS patients and healthy controls, exploring their potential as non-invasive diagnostic tools. Serum samples from CNS patients (n = 6) and healthy controls (n = 26) were analyzed using quantitative real-time polymerase chain reaction. While both lncRNAs showed decreased expression in CNS patients compared to controls, the differences were not statistically significant. However, receiver operating characteristic curve analysis revealed promising diagnostic performances for both lncRNAs. Correlations between lncRNA expression and clinical parameters were explored, revealing potential associations with disease progression. Overall, this study provides preliminary insights into the role of lncRNAs HOTTIP and HOTAIR in CNS and underscores the need for further research to validate their utility as biomarkers and therapeutic targets in this rare disorder.

#2723 10-hydroxy-trans-2-decenoic and nonanoic acid delayed senescence in adult renal progenitor cells and increased the anti-aging Klotho protein secretion

Abstract Background and Aims Recent investigations have elucidated the complex system involving human adult renal stem/progenitor cells (ARPCs) and their pivotal role in maintaining homeostasis and in facilitating regenerative processes within the adult kidneys. CD133+/CD24+ ARPCs can repair several kinds of renal damage but their reparative properties can be compromised by the cell senescence, contributing to renal aging and impaired damage repair. The functional marker CD133 inversely correlates with cellular senescence and plays a crucial role in the ARPC regulation. Decreased protective factors, hypoxia, and microenvironmental stress drive increasingly cell senescence, disordered inflammation and renal fibrosis. The resulting fibrosis, senescence, and microvascular rarefaction exacerbate damage and promote chronic kidney disease (CKD) progression. In this study, we explore the impact of natural molecular compounds and drugs on slowing down and delaying ARPC senescence. Method ARPCs were treated with the following compounds for 48 hours: nonanoic acid (1 mM), 3-decenoic acid (1 mM), 10-hydroxy-trans-2-decenoic acid (10-HDA, 25uM), and Valproic acid (VPA, 1 mM), either individually or in combination. Lipid microvesicles were used to transmit the bioactive molecules. FACS was used to determine the CD133 levels. the β-galactosidase assays were used to determine cell senescence status. Western blots were performed to assess p16, p53 and p21 markers. Results Cytofluorimetry results demonstrated an increase in the expression of CD133, the inverse cell senescence marker, both following stimulation with decenoic (fold change = 1.8, p = 0.0053) and nonanoic acid (FC = 1.3, p = 0.0056), and with VPA (FC 2, p = 0.0036). Simultaneously, the number of senescent cells decreased, as confirmed by the β-galactosidase assay (FC = 0.13, p = 0.0005). The treatment with decenoic and nonanoic acid also restored high levels of the lncRNA HOTAIR (FC = 14.6 for nonanoic acid and 12.7 for 10-HDA; p = 0.05), that in turn promoted the secretion of the α-Klotho anti-aging protein (FC = 3.1; p = 0.01). Additionally, the western blot analysis revealed that the 10-HDA decreased the expression of cell senescence markers, p16 (FC = 1.6, p = 0.05), p53 (FC = 1.8, p = 0.05) and p21 (FC= 3.7, p = 0.05). Moreover, the nonanoic acid reduced the expression of p16 (FC = 1.8, p = 0.05), p53 (FC = 2, p = 0.05) and p21 (FC= 2.6, p = 0.0007). Also, their combination contributes to decrease p16 (FC = 1.9, p = 0.05), p53 (FC = 1.3, p = 0.05) and p21 (FC= 2.5, p = 0.05). Conclusion This study identifies specific molecules capable of reducing or delaying ARPC senescence. In particular, the two natural compounds 10-HDA and nonanoic acid can also enhance the capacity of renal progenitors to secrete the α-Klotho protein whose decline prevention by several mechanisms can attenuate renal injuries, retard CKD progression, ameliorate extrarenal complications, and improve renal function. These findings present potential therapeutic avenues for delaying or mitigating the progression of CKD.

HYPOXIA induces lncRNA HOTAIR for recruiting RELA in papillary thyroid cancer cells to upregulate miR-181a and promote angiogenesis.

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. 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. 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. HOTAIR activated RELA to upregulate miR-181a during hypoxia. Exosomal miR-181a promotes tumor angiogenesis by downregulating GATA6.

Discovery and functional characterization of LncRNAs associated with inflammation and macrophage activation

Long noncoding RNAs (lncRNA) are emerging players in regulation of gene expression and cell signaling and their dysregulation has been implicated in a multitude of human diseases. Recent studies from our laboratory revealed that lncRNAs play critical roles in cytokine regulation, inflammation, and metabolism. We demonstrated that lncRNA HOTAIR, which is a well-known regulator of gene silencing, plays critical roles in modulation of cytokines and proinflammatory genes, and glucose metabolism in macrophages during inflammation. In addition, we recently discovered a series of novel lncRNAs that are closely associated with inflammation and macrophage activation. We termed these as long-noncoding inflammation associated RNAs (LinfRNAs). We are currently engaged in the functional characterization of these hLinfRNAs (human LinfRNAs) with a focus on their roles in inflammation, and we are investigating their potential implications in chronic inflammatory human diseases. Here, we have summarized experimental methods that have been utilized for the discovery and functional characterization of lncRNAs in inflammation and macrophage activation.

Exploration of the association between HIF3α mRNA and lncRNA MALAT1 in laryngeal squamous cell carcinoma by correlation analysis.

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 RNA HOTAIR: from pan-cancer analysis to colorectal cancer-related uridine metabolism.

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.

Retraction: lncRNA HOTAIR promotes gastric cancer proliferation and metastasis via targeting miR-126 to active CXCR4 and RhoA signaling pathway.

Retraction: Jun Xiao, Hao Lai, Sheng-Hong Wei, Zai-Sheng Ye, Fu-Sheng Gong, Lu-Chuan Chen (2019), lncRNA HOTAIR promotes gastric cancer proliferation and metastasis via targeting miR-126 to active CXCR4 and RhoA signaling pathway. Cancer Med, 8: 6768-6779. https://doi.org/10.1002/cam4.1302 The above article, published online on 13 September 2019, and a corresponding Corrigendum (https://doi.org/10.1002/cam4.4435), published online on 22 November 2021, in Wiley Online Library (wileyonlinelibrary.com) have been retracted by agreement between the journal's Editor-in-Chief, Stephen Tait, and John Wiley & Sons Ltd. Following publication, concerns were raised by a third party regarding duplication of images included within Figures3C and 5E. Furthermore, these figures have previously been published elsewhere, identifying the cells as originating from different cell lines and subjected to different treatment. The authors did not respond to the concerns raised and did not provide the original data. The editors consider the results and conclusion reported in this article unreliable.

Long-Noncoding-RNA HOTAIR Upregulation is Associated with Poor Breast Cancer Outcome: A Systematic Review and Meta Analysis.

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. 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. 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). Upregulation of lncRNA HOTAIR is associated with worse DFS aand MFS that can potentially be used as a prognostic marker in breast cancer patients.