Histone modification-linked prognostic model for ovarian cancer reveals LBX2 as a novel growth promoter.

Ovarian cancer (OC) is a deadly disease with limited treatment options and poor overall survival rates. This study aimed to investigate the role of histone modification-related genes in predicting the prognosis of OC patients. Transcriptome data from multiple cohorts, including bulk RNA-Seq data and single-cell scRNA-Seq data, were collected. Gene set enrichment analysis was used to identify enriched gene sets in the histone modification pathway. Differentially expressed genes (DEGs) between histone modification-high and histone modification-low groups were identified using Lasso regression. A prognostic model was constructed using five selected prognostic genes from the DEGs in the TCGA-OV cohort. The study found enrichment of gene sets in the histone modification pathway and identified five prognostic genes associated with OC prognosis. The constructed risk score model based on histone modification-related genes was correlated with immune infiltration of T cells and M1 macrophages. Mutations are more prevalent in the high-risk group compared to the low-risk group. Several drugs were screened against the model genes. Through in vitro experiments, we confirmed the expression patterns of the model genes. LBX2 facilitates the proliferation of OC. Histone modification-related genes have the potential to serve as biomarkers for predicting OC prognosis. Targeting these genes may lead to the development of more effective therapies for OC. Additionally, LBX2 represents a novel cell proliferation promoter in OC carcinogenesis.

Long noncoding RNA LBX2-AS1 promotes colorectal cancer progression via binding with PTBP1 and stabilizing KAT2A expression.

The long noncoding RNAs (lncRNAs) have been investigated in colorectal cancer (CRC). The aim of this study is to identify the biological functions of LBX2-AS1 in CRC. Quantitative real-time polymerase chain reaction was used to examine the expression of LBX2-AS1 in CRC cells. Cell counting kit-8 and colony formation assays were performed to examine cell proliferation. Wound healing and transwell invasion assays were performed to examine the cell migration and invasion. The interaction between PTBP1 and LBX2-AS1 or KAT2A was confirmed by RNA immunoprecipitation. The KAT2A messenger RNA (mRNA) stability was probed using the transcriptional inhibitor Actinomycin D. LBX2-AS1 was significantly increased in CRC tissues and cells. Knockdown of LBX2-AS1 inhibited CRC cell proliferation, migration, and invasion. The notch signaling pathway was activated by LBX2-AS1. LBX2-AS1 enhanced the mRNA stability of the histone acetyltransferase KAT2A by interacting with RNA-binding protein PTBP1. LBX2-AS1 acted as an oncogene in CRC.

LBX2-AS1 promotes ovarian cancer progression by facilitating E2F2 gene expression via miR-455-5p and miR-491-5p sponging.

LBX2-AS1 is a long non-coding RNA that facilitates the development of gastrointestinal cancers and lung cancer, but its participation in ovarian cancer development remained uninvestigated. Clinical data retrieved from TCGA ovarian cancer database and the clinography of 60 ovarian cancer patients who received anti-cancer treatment in our facility were analysed. The overall cell growth, colony formation, migration, invasion, apoptosis and tumour formation on nude mice of ovarian cancer cells were evaluated before and after lentiviral-based LBX2-AS1 knockdown. ENCORI platform was used to explore LBX2-AS1-interacting microRNAs and target genes of the candidate microRNAs. Luciferase reporter gene assay and RNA pulldown assay were used to verify the putative miRNA-RNA interactions. Ovarian cancer tissue specimens showed significant higher LBX2-AS1 expression levels that non-cancerous counterparts. High expression level of LBX2-AS1 was significantly associated with reduced overall survival of patients. LBX2-AS1 knockdown significantly down-regulated the cell growth, colony formation, migration, invasion and tumour formation capacity of ovarian cancer cells and increased their apoptosis in vitro. LBX2-AS1 interacts with and thus inhibits the function of miR-455-5p and miR-491-5p, both of which restrained the expression of E2F2 gene in ovarian cancer cells via mRNA targeting. Transfection of miRNA inhibitors of these two miRNAs or forced expression of E2F2 counteracted the effect of LBX2-AS1 knockdown on ovarian cancer cells. LBX2-AS1 was a novel cancer-promoting lncRNA in ovarian cancer. This lncRNA increased the cell growth, survival, migration, invasion and tumour formation of ovarian cancer cells by inhibiting miR-455-5p and miR-491-5p, thus liberating the expression of E2F2 cancer-promoting gene.

LncRNA LBX2-AS1 promotes colorectal cancer progression and 5-fluorouracil resistance.

BACKGROUND: Recent reports suggest that the long non-coding RNA LBX2 antisense RNA 1 (LBX2-AS1) acts as an important regulator in cancer progression, but its significance in colorectal cancer (CRC) remains undetermined. METHODS: LBX2-AS1 expression levels in CRC were determined from the GEPIA database and CRC tissues to investigate clinical relevance. meRIP-PCR assays investigated the molecular mechanisms underlying the function of m6A in LBX2-AS1. Loss of function experiments was used to define the role of LBX2-AS1 in the progression of CRC. The ceRNA function of LBX2-AS1 was evaluated by RNA immunoprecipitation. In vitro and PDX models were used to determine if LBX2-AS1 promotes 5-fluorouracil resistance. RESULTS: Data from the TCGA and our institutional patient cohorts established that LBX2-AS1 levels were significantly upregulated in most CRC tissues relative to normal adjacent colon tissues. Moreover, LBX2-AS1 levels were positively correlated with aggressive disease characteristics, constituting an independent prognostic indicator of overall patient survival. Mechanistic investigations suggested that the increased LBX2-AS1 in CRC was mediated by METTL3-dependent m6A methylation. In vitro experiments indicated that knockdown of LBX2-AS1 inhibited CRC proliferation, migration and invasion with this phenotype linked to LBX2-AS1-mediated regulation of AKT1, acting as a ceRNA to sponge miR-422a. Ex vivo analysis of patient-derived CRC xenografts showed that low LBX2-AS1 expression cases exhibited 5-FU responsiveness and clinical investigations confirmed that low LBX2-AS1 expression was associated with improved clinical benefits from 5-FU therapy. CONCLUSIONS: Together these results suggest that LBX2-AS1 may serve as a therapeutic target and predictor of 5-FU benefit in CRC patients.

Silencing of lncRNA LBX2-AS1 suppresses glioma cell proliferation and metastasis through the Akt/GSK3ß pathway in vitro.

Long non-coding RNAs (lncRNAs) have been proposed to play pivotal roles in the tumorigenesis of various malignant tumors. Previous studies have found that lncRNA LBX2-AS1 is involved in the progression of various tumors. However, currently, the expression and exact mechanism of LBX2-AS1 in glioma remain unclear. In this study, using online-available datasets combined with clinical glioma tissues collected, we found that LBX2-AS1 was significantly increased and negatively correlated with prognosis in glioma. In vitro functional assays such as CCK-8, Annexin V, transwell assay, and western blot analysis showed that silencing of LBX2-AS1 suppressed the proliferation, migration, and invasion of glioma cells and increased apoptosis. RNA sequencing and western blot analysis confirmed that LBX2-AS1 regulates the Akt/GSK3ß pathway. In conclusion, this study showed that lncRNA LBX2-AS1 depletion inhibits the proliferation, migration, and invasion of glioma cells and increases apoptosis through the Akt/GSK3ß pathway. lncRNA LBX2-AS1 is expected to become a new target for glioma therapy.

LBX2-AS1 up-regulated by NFIC boosts cell proliferation, migration and invasion in gastric cancer through targeting miR-491-5p/ZNF703.

BACKGROUND: The crucial role of long non-coding RNAs (lncRNAs) has been certified in human cancers. The lncRNAs with abnormal expressions could act as tumor inhibitors or oncogenes in the advancement of tumors. LBX2-AS1 was once reported to accelerate esophageal squamous cell carcinoma. Nonetheless, its function in gastric cancer (GC) remained a riddle. METHODS: RT-qPCR was used to examine the expression of NFIC/LBX2-AS1/miR-491-5p/ZNF703 in GC cell lines. The functions of LBX2-AS1 in GC were appraised by colony formation, EdU, flow cytometry analysis, transwell and wound healing assays. Luciferase reporter, ChIP and RNA pull down assays were utilized to evaluate the interactions among genes. RESULTS: LBX2-AS1 was up-regulated in GC cell lines. Knockdown of LBX2-AS1 repressed the proliferative, migratory, and invasive abilities of GC cells. Moreover, LBX2-AS1 was transcriptionally activated by NFIC. And LBX2-AS1 could bind with miR-491-5p. Besides, miR-491-5p depletion or ZNF703 upregulation could counteract the repressing effects of LBX2-AS1 silence on GC progression. CONCLUSION: In a word, LBX2-AS1 up-regulated by NFIC promoted GC progression via targeting miR-491-5p/ZNF703, implying LBX2-AS1 was an underlying treatment target for GC patients.

Long noncoding RNA LBX2-AS1-modulated miR-4766-5p regulates gastric cancer development through targeting CXCL5.

BACKGROUND: Long noncoding RNAs (LncRNAs) have been reported to critically regulate gastric cancer (GC). Recently, it was reported that LBX2 antisense RNA 1 (LBX2-AS1) is abnormally expressed in GC. However, the role of LBX2-AS1 in the malignancy of GC is worth further discussion. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the LBX2-AS1, miR-4766-5p and C-X-C motif chemokine (CXCL5) expression in GC tissues and cells. Dual-luciferase reporter assay was applied to examine the target relationship between LBX2-AS1 and miR-4766-5p or miR-4766-5p and CXCL5. Cell counting kit-8 (CCK-8) and Transwell assays were used to detect cell proliferation, migration and invasion rates. The protein expression of CXCL5 was confirmed using western blot. The RNA pull down experiment was used to verify the specificity of LBX2-AS1 and miR-4766-5p on BGC-823 and SGC-7901 cells. RESULTS: LBX2-AS1 was up-regulated in GC tissues and cells, and its knockdown suppressed proliferation, migration and invasion of GC cells. While, overexpression of LBX2-AS1 increased proliferation and increased CXCL5 mRNA level. CXCL5 improved cell proliferation, migration and invasion of GC cells. LBX2-AS1 could bind to miR-4766-5p to regulate CXCL5 expression. Overexpression of CXCL5 overturned those effects of miR-4766-5p in GC cells. RNA Pull down shown that BGC-823 and SGC-7901 cells, miR-4766-5p specifically binds to LBX2-AS1. CONCLUSIONS: In short, this study demonstrated that LBX2-AS1 promoted proliferation, migration and invasion through up-regulation CXCL5 mediated by miR-4766-5p in GC. The LBX2-AS1/miR-4766-5p/CXCL5 regulatory axis provides a theoretical basis for the research on lncRNA-directed therapeutics in GC.

Long non-coding RNA LBX2-AS1 enhances glioma proliferation through downregulating microRNA-491-5p.

BACKGROUND: Dysregulation of lncRNAs is frequent in glioma and has emerged as an important mechanism involved in tumorigenesis. Previous analysis of Chinese Glioma Genome Atlas (CGGA) database indicated that LBX2-AS1 expression is one of differentially expression lncRNA between lower grade glioma (LGG) (grade II and III) and glioblastoma multiforme (GBM). However, the function and mechanism of LBX2-AS1 in glioma has not been evaluated yet. METHODS: Here, we analyzed the expression of LBX2-AS1 in GTEx data (normal brain), TCGA-LGG and TCGA-GBM. RT-PCR was performed to detect LBX2-AS1 in surgery obtained normal brain and glioma. CCK-8 kit and Annexin V-FITC-PI Apoptosis Detection Kit were used to study the function of LBX2-AS1 on glioma proliferation and apoptosis. Bioinformatic analysis, RNA immunoprecipitation, RT-PCR, western blotting and dual luciferase reporter assay were carried out to investigate the target miRNA of LBX2-AS1. The discovered mechanism was validated by the rescue assay. RESULTS: Following study of GTEx and TCGA data, LBX2-AS1 was significantly elevated in glioma compared with normal brain and in GBM compared with LGG. Higher expression of LBX2-AS1 was associated with poor prognosis of patients with glioma. Expression of LBX2-AS1 was positively correlated with pathology classification of glioma. Knockdown of LBX2-AS1 inhibited cell proliferation and induced cell apoptosis in glioma. LBX2-AS1 have complimentary binding site for tumor suppressor miR-491-5p and we showed that LBX2-AS1 sponged miR-491-5p to upregulate TRIM28 expression in glioma cells. TRIM28 overexpression attenuated the effect of LBX2-AS1 knockdown on glioma cells. CONCLUSIONS: In conclusion, LBX2-AS1 was an increased lncRNA in glioma. Mechanistically, LBX2-AS1 promoted glioma cell proliferation and resistance to cell apoptosis via sponging miR-491-5p.

LBX2-AS1/miR-219a-2-3p/FUS/LBX2 positive feedback loop contributes to the proliferation of gastric cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) are increasingly investigated in numerous carcinomas containing gastric cancer (GC). The aim of our research is to inquire about the expression profile and role of LBX2-AS1 in GC. METHODS: The expressions of LBX2-AS1, miR-219a-2-3p, FUS and LBX2 were measured by qRT-PCR. Western blot evaluated FUS and LBX2 protein levels. Cell proliferation and apoptosis were, respectively, evaluated by CCK-8, colony formation, EdU, flow cytometry and TUNEL assays. FISH and subcellular fractionation assays examined the position of LBX2-AS1. The binding between genes were certified by RIP, RNA pull-down, ChIP and luciferase reporter assays. Pearson correlation analysis analyzed the association of genes. Kaplan-Meier method detected the relationship of LBX2-AS1 expression with overall survival. RESULTS: The up-regulation of LBX2-AS1 in GC tissues and cells was verified. Function assays proved that LBX2-AS1 down-regulation restricted the proliferation ability. Then, we unveiled the LBX2-AS1/miR-219a-2-3p/FUS axis. Additionally, LBX2-AS1 positively regulated LBX2 mRNA stability via FUS. LBX2 transcriptionally modulated LBX2-AS1. In the end, rescue and in vivo experiments validated the whole regulatory mechanism. CONCLUSION: LBX2-AS1/miR-219a-2-3p/FUS/LBX2 positive feedback loop mainly affected the proliferation and apoptosis abilities of GC cells, offering novel therapeutic targets for the treatment of patients with GC.

LBX2-AS1 is activated by ZEB1 and promotes the development of esophageal squamous cell carcinoma by interacting with HNRNPC to enhance the stability of ZEB1 and ZEB2 mRNAs.

Long non-coding RNAs (lncRNAs) are a group of transcripts, which can regulate the progression of esophageal squamous cell carcinoma (ESCC). According to the data of TCGA, Ladybird homeobox 2 antisense RNA 1 (LBX2-AS1) is a highly expressed lncRNA in ESCC samples. Herein, we chose it for further study. Furtherly, dysregulation of LBX2-AS1 was identified in ESCC tissues with metastasis. Loss-of function assays were conducted and revealed that LBX2-AS1 knockdown suppressed ESCC cell migration and epithelial-mesenchymal transition (EMT). Zinc finger E-box binding homeobox 1 (ZEB1) and zinc finger E-box binding homeobox 2 (ZEB2) are two EMT-related transcription factors. Since LBX2-AS1 promoted the EMT progress and simultaneously enhanced the level of ZEB1 and ZEB2, we further investigated whether LBX2-AS1 promoted cell migration and EMT in ESCC by regulating ZEB1 and ZEB2. Mechanism investigations revealed that RNA binding protein heterogeneous nuclear ribonucleoprotein C (HNRNPC) could interact with LBX2-AS1, ZEB1 and ZEB2, simultaneously. The similar function of HNRNPC in regulating migration and EMT process was demonstrated. ZEB1 has been reported as a positive transcriptional regulator of lncRNA. Therefore, further mechanism analysis was made to demonstrate whether ZEB1 could regulate the transcription of LBX2-AS1. Collectively, our data showed that ZEB1-induced upregulation of LBX2-AS1 promoted cell migration and EMT process in ESCC via enhancing the stability of ZEB1 and ZEB2.

LncRNA LBX2-AS1 inhibits acute myeloid leukemia progression through miR-455-5p/MYLIP axis.

Acute myeloid leukemia (AML) is a common blood cancer primarily affecting the bone marrow and blood cells, which is prevalent among adults. Long non-coding RNAs (lncRNAs) have been shown to play a crucial role in the development and progression of AML. LBX2-AS1 is a recently discovered lncRNA that has been linked to the pathogenesis and progression of several types of cancer. This study aimed to investigate the role and possible mechanisms of LBX2-AS1 in AML. Expression levels of LBX2-AS1, miR-455-5p, and their target genes were detected in AML samples and cells by RT-qPCR. Cell proliferation and apoptosis were determined by Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays, and flow cytometry, respectively. LBX2-AS1 was downregulated in AML specimens and cells, and overexpression of LBX2-AS1 significantly inhibited cell proliferation and enhanced apoptosis in vitro. We also determined the effects of LBX2-AS1 overexpression in an AML mouse model by in vivo bioluminescence imaging. Mechanistically, LBX2-AS1 acts as a competitive endogenous RNA, which promotes myosin regulatory light chain interacting protein (MYLIP) expression by sponging miR-455-5p. Knockdown of MYLIP or upregulation of miR-455-5p antagonized the effect of LBX2-AS1 overexpression on the progression of AML. LBX2-AS1 may thus be a valuable therapeutic target for AML.

LncRNA LBX2-AS1 promotes proliferation and migratory capacity of clear cell renal cell carcinoma through mitophagy.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been extensively investigated in the field of cancer, among which, lncRNA ladybird homeobox 2-antisense RNA 1 (LBX2-AS1) has been demonstrated to exert carcinogenic effects on a variety of malignancies. However, the biological functions of LBX2-AS1 in clear cell renal cell carcinoma (ccRCC) have not been explicitly elucidated. METHODS: Arraystar lncRNA chip and qRT-PCR verify the expression of LncRNA LBX2-AS1 in ccRCC. CCK-8 assay and cell cloning assay were used to assess the proliferative capacity of ccRCC cells. Migration abilities were quantified by scratch assay and transwell assay. Potential molecular signaling pathways were determined by high-throughput whole transcriptomics analysis. WB analysis was performed to validate the relationship between LBX2-AS1 and key molecules of mitophagy pathway. The effect of LBX2-AS1 on mitophagy was observed by laser confocal microscopy. Rescue experiments further validated the role of downstream gene FOXO3A in the LBX2-AS1 signaling pathway. Finally, the authentic effect of LBX2-AS1 was verified in vivo. RESULTS: LncRNA LBX2-AS1 was over expressed in ccRCC tissues and could enhance the proliferation and migration of ccRCC cells. Autophagic pathway was identified as a possible mechanism involved in the oncogenic effect of LBX2-AS1. Mitophagy levels were observed in LBX2-AS1 low-expressing cells through laser confocal microscopy. Knockdown of LBX2-AS1 significantly elevated mitophagy levels as observed using laser confocal microscopy and led to FOXOA3 decreasing in and BNIP3L and LC3 enrichment. Meanwhile, LBX2-AS1 knocking down dampened the proliferation of ccRCC cells in vivo.

Long non-coding RNA LBX2-AS1 activates IL4R to promote glioblastoma metastasis and angiogenesis by binding to the transcription factor NFKB1.

INTRODUCTION: LncRNA LBX2-AS1 drives the development of various cancers, but the exact mechanism whereby LBX2-AS1 affects glioblastoma (GBM) progression is unaddressed. This study intended to delineate the regulatory mechanism of LBX2-AS1 in GBM metastasis and angiogenesis. MATERIAL AND METHODS: LBX2-AS1 level in GBM was assessed by bioinformatics methods. The lncRNA-transcription factor (TF)-mRNA trios were predicted using the lncMAP database. Correlation between genes was predicted by Pearson analysis. The binding relationship was predicted by JASPAR. Levels of LBX2-AS1 and its downstream genes were assayed via qRT-PCR. Changes in expressions of VEGF-A, IL4R, and epithelial-mesenchymal transition (EMT)-associated proteins were assessed through western blot. GBM cell proliferation, migration, and invasion were assayed through CCK8, colony formation, and Transwell experiments. In vitro angiogenesis capacity was evaluated via a HUVEC tube formation experiment. The regulatory relationship between various genes was verified through radioimmunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and dual-luciferase assays. RESULTS: LBX2-AS1 was elevated in GBM, and in vitro experiments demonstrated the stimulatory effect of LBX2-AS1 on GBM cell proliferation, invasion, migration, and angiogenesis. We observed that LBX2-AS1 activated IL4R expression by binding the transcription factor NFKB1, thus promoting the progression of GBM. Rescue experiments illustrated that silencing IL4R or NFKB1 reversed the impact of forced LBX2-AS1 expression on GBM cells. CONCLUSIONS: This study revealed the mechanism of the LBX2-AS1/NFKB1/IL4R axis in driving GBM metastasis and angiogenesis, which may help to improve the regulatory network of GBM malignant progression and provide potential targets for GBM treatment.

The role of LncRNA LBX2-AS1 in cancers: functions, mechanisms and potential clinical utility.

Increasingly advanced biology technique has revealed that long non-coding RNAs (lncRNA) as critical factors that exert significant regulatory effects on biological functions by modulating gene transcription, epigenetic modifications and protein translation. A newly emerging lncRNA, ladybird homeobox 2 (LBX2)-antisense RNA 1 (LBX2-AS1), was found to be highly expressed in various tumors. Moreover, it is functionally linked to the regulation of essential tumor-related biological processes, such as cell proliferation and apoptosis, through interactions with multiple signaling molecules/pathways. The important roles played by LBX2-AS1 in cancer initiation and progression suggest that this lncRNA has enormous clinical potential for use as a novel biomarker or therapeutic target. In this article, we retrospectively review the latest advances in research exploring the roles of the lncRNA LBX2-AS1 in oncology field, highlighting its involvement in a comprehensive network of molecular mechanisms underlying diverse cancers and examining its potential applications in clinical practice.

LncRNA LBX2-AS1 impacts osteosarcoma sensitivity to JQ-1 by sequestering miR-597-3p away from BRD4.

Objective: Recent knowledge concerning the significance of long non-coding RNA (lncRNA)-mediated ceRNA networks provides new insight into their possible roles as specific biomarkers for the treatment of osteosarcoma (OS). Thus, this study aims to clarify the functional relevance and mechanistic actions of lncRNA LBX2-AS1 in OS. Methods: Differential analysis was performed by integrating the TCGA and GTEx databases. Cox regression analysis was then employed to assess the prognostic value of the model. The expression of lncRNA LBX2-AS1 and miR-597-3p was quantified in OS cell lines by qRT-PCR. The proliferation, migration, invasion, and apoptosis of OS cell lines in response to manipulated lncRNA LBX2-AS1 were evaluated by MTT, colony formation, transwell, Western blot, and flow cytometry assays. Luciferase activity was assayed to validate the reciprocal regulation between lncRNA LBX2-AS1 and miR-597-3p. The protein levels of BRD4 and EMT-related factors were examined by Western blot assay. Finally, tumor growth in response to LBX2-AS1 knockdown was evaluated in xenograft-bearing nude mice. Results: By integrating the GTEx and TCGA databases, we identified 153 differentially expressed lncRNAs. Among them, 5 lncRNAs, RP11-535M15.1, AC002398.12, RP3-355L5.4, LBX2-AS1, and RP11.47A8.5, were selected to establish a model, which predicted the prognosis of OS. Higher lncRNA LBX2-AS1 expression was noted in OS tissues relative to that in normal tissues. Silencing lncRNA LBX2-AS1 facilitated apoptosis and curtailed proliferative, migratory, and invasive capacities of OS cells. Mechanistically, lncRNA LBX2-AS1 could elevate the expression of BRD4, an oncogene, by competitively binding to miR-597-3p. More importantly, knockdown of lncRNA LBX2-AS1 increased the sensitivity of OS cells to the BRD4 inhibitor JQ-1. Finally, the tumor growth of OS cell xenografts was constrained in vivo in the presence of lncRNA LBX2-AS1 knockdown. Conclusion: In conclusion, lncRNA LBX2-AS1 promotes the growth of OS and represses the sensitivity to JQ-1 by sponging miR-597-3p to elevate the expression of BRD4.

Long non-coding RNA LBX2-AS1 predicts poor survival of colon cancer patients and promotes its progression via regulating miR-627-5p/RAC1/PI3K/AKT pathway.

Colon cancer is one of the most prevalent malignant tumors across the world. Increasing studies have demonstrated that long non-coding RNAs (lncRNAs) take part in colon cancer development. Our study intends to explore the expression characteristics of LBX2-AS1, a novel lncRNA, in colon cancer and its underlying mechanisms. The results illustrated that LBX2-AS1 level was substantially increased in colon cancer tissues and was obviously correlated with the tumor volume and early distant metastasis of patients. Besides, overexpression of LBX2-AS1 remarkably boosted growth, proliferation, and metastasis and restrained apoptosis in colon cancer cells, whereas LBX2-AS1 knockdown produced the opposite effect. On the other hand, miR-627-5p, down-regulated in colon cancer tissues, was negatively associated with LBX2-AS1 expression. Functional experiments showed that miR-627-5p suppressed colon cancer growth. Mechanistically, LBX2-AS1, as an endogenous competitive RNA, targeted miR-627-5p and restrained its expression, while miR-627-5p targeted and negatively regulated the RAC1/PI3K/AKT axis. Collectively, this study has revealed that LBX2-AS1 is a poor prognostic factor of colon cancer and can regulate colon cancer progression by regulating the miR-627-5p/RAC1/PI3K/AKT pathway.

LBX2-AS1 as a Novel Diagnostic Biomarker and Therapeutic Target Facilitates Multiple Myeloma Progression by Enhancing mRNA Stability of LBX2.

Objective: Multiple myeloma (MM) represents a common age-associated malignancy globally. The function and underlying mechanism of antisense lncRNA LBX2-AS1 remain ambiguous in multiple myeloma (MM). Herein, we aimed to observe the biological implication of this lncRNA in MM. Methods: RT-qPCR was employed to examine circulating LBX2-AS1 and LBX2 in 60 paired MM and healthy subjects. Correlation between the two was analyzed by Pearson test. Under transfection with shLBX2-AS1, proliferation and apoptosis were evaluated in MM cells through CCK-8, colony formation and flow cytometry. LBX2 expression was examined in MM cells with shLBX2-AS1 or pcDNA3.1-LBX2 transfection. Following treatment with cycloheximide or actinomycin D, LBX2 expression was examined in pcDNA3.1-LBX2-transfected MM cells at different time points. Rescue assays were then presented. Finally, xenograft tumor models were established. Results: Circulating LBX2-AS1 was up-regulated in MM patients and positively correlated to LBX2 expression. Area under the curve (AUC) of LBX2-AS1 expression was 0.7525. Its up-regulation was also found in MM cells and primarily distributed in cytoplasm. LBX2-AS1 knockdown distinctly weakened proliferative ability and induced apoptosis in MM cells. Overexpressing LBX2-AS1 markedly strengthened LBX2 expression by increasing its mRNA stability. Rescue assays showed that silencing LBX2-AS1 distinctly weakened the pcDNA3.1-LBX2-induced increase in proliferation and decrease in apoptosis for MM cells. Silencing LBX2-AS1 markedly weakened tumor growth. Conclusion: Our data demonstrated that circulating LBX2-AS1 could be an underlying diagnostic marker in MM. Targeting LBX2-AS1 suppressed tumor progression by affecting mRNA stability of LBX2 in MM. Hence, LBX2-AS1 could be a novel therapeutic marker against MM.

Overexpression of Long Noncoding RNA LBX2-AS1 Promotes the Proliferation of Colorectal Cancer.

BACKGROUND: LBX2 antisense RNA 1 (LBX2-AS1), a long noncoding RNA, has been identified to be closely associated with the progression of various cancers. However, the role of LBX2-AS1 in colorectal cancer (CRC) is still poorly understood. In this study, we aimed to investigate the expression and function of LBX2-AS1 in CRC. MATERIAL AND METHODS: Expression data from the Gene Expression Omnibus (GEO) and Gene Expression Profiling Interactive Analysis (GEPIA) databases and results obtained from clinical samples/patients were used to determine the correlation between LBX2-AS1 expression and pathological stages, overall survival (OS). Furthermore, knockdown of LBX2-AS1 in CRC cells using the short interfering RNA (siRNA) technique, and observed its biological functions using western blotting, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), cell counting kit-8 (CCK-8) and flow cytometry assay in the CRC cell line. RESULTS: Our study demonstrated that the expression levels of LBX2-AS1 were higher in CRC cell lines than in normal colon mucosal cell lines. Bioinformatics analysis revealed that CRC patients with high LBX2-AS1 expression levels had poor OS. Furthermore, knockdown of LBX2-AS1 in CRC cells could attenuate the proliferative ability of CRC cells in vitro, which is associated with decreased expression of cyclin-dependent kinase (CDK) 3, CDK6, and CCND1 and enhanced expression of cyclin-dependent kinase inhibitor 1A. CONCLUSIONS: LBX2-AS1 plays a crucial role in the tumorigenesis of CRC, providing a potential therapeutic target for CRC patients.

ELK1­mediated upregulation of lncRNA LBX2­AS1 facilitates cell proliferation and invasion via regulating miR­491­5p/S100A11 axis in colorectal cancer.

The aim of the present study was to investigate the role and regulatory mechanism of LBX2 antisense RNA 1 (LBX2­AS1) in colorectal cancer. Firstly, LBX2­AS1 expression was detected using reverse transcription­quantitative PCR in colorectal cancer tissues and cells, and its prognostic and diagnostic efficacy was assessed in a colorectal cancer cohort (n=145). Subcellular fractionation assay of LBX2­AS1 was performed. Secondly, the effects of LBX2­AS1 and microRNA (miR)­491­5p on colorectal cancer cell proliferation, apoptosis, migration and invasion were investigated by a series of functional assays. Thirdly, RNA immunoprecipitation, dual­luciferase reporter and gain and loss of function assays were carried out to analyze the interactions between ETS transcription factor ELK1 (ELK1) and LBX2­AS1, as well as LBX2­AS1, miR­491­5p and S100A11. The results showed that LBX2­AS1 was upregulated both in colorectal cancer tissues and cells, which was distributed in the cytoplasm and nucleus of colorectal cancer cells. Clinically, high LBX2­AS1 expression could be an independent prognostic factor for colorectal cancer. Furthermore, relative operating characteristic curve analysis showed that LBX2­AS1 was a sensitive diagnostic marker for colorectal cancer. Highly expressed ELK1, as a transcription factor, could bind to the two conserved sites in the promoter region of LBX2­AS1, thereby activating the transcription of LBX2­AS1. Silencing LBX2­AS1 markedly inhibited proliferative, migratory and invasive abilities of colorectal cancer cells. miR­491­5p expression was downregulated, while S100A11 expression was upregulated in colorectal cancer tissues and cells. Dual­luciferase reporter assays confirmed that LBX2­AS1 could block S100A11 degradation via competitively binding to miR­491­5p. Furthermore, LBX2­AS1 overexpression could notably reverse the inhibitory effect of miR­491­5p on proliferation and invasion of colorectal cancer cells. Taken together, LBX2­AS1 induced by transcription factor ELK1 may facilitate colorectal cancer cell proliferation and invasion via regulation of the miR­491­5p/S100A11 axis. Thus, LBX2­AS1 could be an underlying prognostic and diagnostic marker for colorectal cancer.

SP1-upregulated LBX2-AS1 promotes the progression of glioma by targeting the miR-491-5p/LIF axis.

Background: Mounting evidences have shown the importance of lncRNAs in carcinogenesis and cancer progression. LBX2-AS1 is identified as an oncogenic lncRNA that is abnormally expressed in gastric cancer and lung cancer samples. This study aims to explore the potential role of LBX2-AS1 in regulating proliferation and EMT in glioma, and the underlying mechanism. Methods: Relative levels of LBX2-AS1 in glioma samples and cell lines were detected by qRT-PCR and FISH. In vivo and in vitro regulatory effects of LBX2-AS1 on proliferation and EMT were examined in the xenograft glioma model and glioma cells. The interaction between SP1 and LBX2-AS1 was assessed by ChIP. Through bioinformatic analyses, dual-luciferase reporter assay, RIP and Western blot, the regulation of LBX2-AS1 and miR-491-5p on the target gene LIF was identified. Results: LBX2-AS1 was upregulated in glioma samples and cell lines, and its transcription was promoted by binding to the transcription factor SP1. As a lncRNA mainly distributed in the cytoplasm, LBX2-AS1 sponge miR-491-5p to further upregulate LIF. The subsequent activated LIF/STAT3 signaling was responsible for promoting proliferation and EMT in glioma. Conclusion: LBX2-AS1 is upregulated by SP1 in glioma, which promotes the progression of glioma by targeting the miR-491-5p/LIF axis. In view of this, LBX2-AS1 is suggested as a novel diagnostic biomarker and therapeutic target of glioma.