LINC01123 potentially correlates with radioresistance in glioma through the miR-151a/CENPB axis.

Radiotherapy represents the most effective nonsurgical therapy, whereas acquired radioresistance remains a major challenge in glioma treatment. Deregulation of long noncoding RNAs (lncRNAs) is frequently involved in tumorigenesis. This study investigates the role of LINC01123 in radioresistance in glioma with molecules involved. LINC01123 was identified as the most upregulated gene in a glioma gene expression dataset GSE103227. LINC01123 was highly expressed in the radioresistant glioma tissues radioresistant glioma U251 (U251R) cells. Downregulation of LINC01123 reduced cell proliferation and colony formation abilities, as well as resistance to apoptosis of the U251R cells after 4 Gy X-ray irradiation. The micro(mi)RNA-151a gene (miR-151a) was a poorly expressed miRNA in glioma, and it was a target of LINC01123. The centromere protein B gene (CENPB) mRNA was a direct target of miR-151a and demonstrated a positive correlation with LINC01123 in glioma tissues and cells. Further inhibition of miR-151a or overexpression of CENPB restored radioresistance of glioma cells. In addition, silencing of LINC01123 suppressed growth of xenograft tumors formed by U251R cells in nude mice. To conclude, the present study demonstrates that LINC01123 serves as a sponge for miR-151a and upregulates CENPB expression to increase the radioresistance of glioma cells in vitro and in vivo.

LINC01123 enhances osteosarcoma cell growth by activating the Hedgehog pathway via the miR-516b-5p/Gli1 axis.

The lncRNA LINC01123 has been reported to act as an oncogene in many human cancers. Nevertheless, the function and underlying mechanism of LINC01123 in osteosarcoma (OS) remain unclear. This study aimed to explore the roles and mechanisms of LINC01123 in OS progression. In this study, the expression of LINC01123 was significantly upregulated in OS cell lines than in a human osteoblast cell line. Furthermore, in vitro and in vivo experiments confirmed that knockdown of LINC01123 suppressed cell progression. Mechanistically, LINC01123 acted as a competing endogenous RNA by sponging miR-516b-5p, thus, increasing Gli1 expression by directly targeting its 3'UTR. Taken together, LINC01123 enhances OS proliferation and metastasis via the miR-516b-5p/Gli1 axis. Therefore, LINC01123 may be a potential therapeutic target for OS treatment.

FOXC1-induced LINC01123 acts as a mediator in triple negative breast cancer.

BACKGROUND: MicroRNAs (miRNAs) representing a subclass of non-coding RNAs are dynamically expressed and participate in multiple pathological responses, whereas, the expression pattern or function of miRNAs has not been fully addressed in triple-negative breast cancer (TNBC). Currently we concentrate on dissecting the probable role of microRNA-663a (miR-663a) in TNBC cellular processes. METHODS: qRT-PCR detected the expression of miR-663a in TNBC cells. Besides, we monitored the effects of miR-663a on TNBC proliferation and apoptosis. On the basis of bioinformatics assistance and mechanical validation, we identified the miRNA-sponging role of LINC01123 and downstream target of miR-663a in TNBC was assessed and verified. The transcription activation of was explored via ChIP and luciferase reporter assays. RESULTS: In comparison to MCF-10A, we certified the downregulation of miR-663a in TNBC cell lines. Augmentation of miR-663a was anti-proliferation and pro-apoptosis in TNBC cell lines. LINC01123 protected CMIP against miR-663a suppression through acting as a sponge of miR-663a in TNBC. LINC01123 was transcriptionally induced by FOXC1. Rescue experiment proved that miR-663a suppression or CMIP (c-Maf inducing protein) enhancement could countervail LINC01123 depletion-mediated effects on TNBC cellular processes. CONCLUSION: LINC01123, activated by FOXC1, regulated TNBC growth through miR-663a/CMIP signaling, which unveiled a new functional pathway of FOXC1-induced LINC01123/miR-663a/CMIP in TNBC.

Diagnostic value and clinical significance of lncRNA LINC01123 combined with fibrinogen in acute cerebral infarction.

OBJECTIVE: To explore the diagnostic value and clinical significance of lncRNA LINC01123 (LINC01123) binding fibrinogen in acute cerebral infarction (ACI) by evaluating the expression and potential molecular mechanism of LINC01123 in patients with acute cerebral infarction. METHODS: The clinical data of all the volunteers were collected. The level of serum LINC01123 in ACI patients was detected by RT-qPCR. The relationship between LINC01123 and fibrinogen was studied via Pearson's correlation analysis. ROC curve was used to evaluate the diagnostic value of LINC01123 and fibrinogen for ACI. The risk factors of ACI were investigated by Binary Logistic regression analysis. And the targeting relationship between LINC01123 and downstream miR-361-3p was verified through luciferase activity assay. RESULTS: Serum LINC01123 and fibrinogen levels were upregulated in ACI patients compared with healthy controls (P < 0.001), and there was a positive correlation between them (r = 0.6537, P < 0.001). In predicting the occurrence of ACI, LINC01123 and fibrinogen have high diagnostic value, and the AUC of combined diagnosis was 0.961, and the sensitivity and specificity (92.54%, 85.82%) were more significant. Meanwhile, LINC01123 and fibrinogen were confirmed to be independent risk factors for ACI (P < 0.0001). Mechanistically, miR-361-3p is the target of LINC01123. The expression of miR-361-3p was low in the serum of ACI patients, which was negatively correlated with the LINC01123 expression (r = -0.6885, P < 0.0001). CONCLUSION: LINC01123 combined with fibrinogen may have important reference value in the diagnosis of ACI as serum markers, which may become clinical indicators to predict the occurrence of ACI.

LncRNA LINC01123 promotes malignancy of ovarian cancer by targeting hsa-miR-516b-5p/VEGFA.

BACKGROUND: Long non-coding RNAs (lncRNAs) play a critical role in the development of ovarian cancer (OC). OBJECTIVE: The study aimed to determine the role of LncRNA LINC01123 in OC bio-progression, which is upregulated in OC tissues during OC progression. METHODS: Bioinformatics methods, GEPIA, and qRT-PCR were used to reveal the level and correlation of LINC01123, hsa-miR-516b-5p, and VEGFA, in OC cell lines. MTT, EdU, TUNEL, and Transwell assays were performed to assess the bioactivity of OC cell. Target sites of LINC01123 and hsa-miR-516b-5p were predicted using Starbase, and the potential linkage points of VEGFA and hsa-miR-516b-5p were predicted using TargetScan. These sites and linkage points were confirmed by double luciferase reporter assay. RESULTS: LINC01123 was upregulated in OC cell lines and LINC01123 silencing suppressed the proliferation and metastasis of OC cells, but promoted cell apoptosis. hsa-miR-516b-5p was linked to LINC01123 and. VEGFA was downstream of hsa-miR-516b-5p. Importantly, silencing of hsa-miR-516b-5p reversed the inhibitory impact of si-LINC01123. The result of hsa-miR-516b-5p inhibitor + si-LINC01123 co-transfection were rescued by si-VEGFA. CONCLUSION: LINC01123 promotes OC development by dampening miR-516b-5p function, and may be a novel target for treating OC.

Long non-coding RNA LINC01123 promotes cell proliferation, migration and invasion via interacting with SRSF7 in colorectal cancer.

BACKGROUND: Increasing evidences demonstrated that long non-coding RNAs (lncRNAs) participates in the occurrence and development of cancer. In this study, we explored the function and molecular mechanism of LINC01123 in colorectal cancer progression. METHODS: Analyze the expression level of LINC01123 in gastrointestinal tumors via TCGA database. Colorectal tumor tissues and normal tissues were collected to detect the expression of LINC01123 by RT-qPCR. CCK-8 assay, clone formation assay, transwell assay, and wound healing assays were used to explore the effects of LINC01123 on the proliferation, invasion and migration of colorectal cancer cells. Coomassie blue staining, RNA pull-down and mass spectrometry were used to screen the protein interacted with LINC01123. Xenograft model was used to explore the effect of LINC01123 in vivo. RESULTS: LINC01123 was up-regulated in colorectal cancer tumor tissues. The proliferation, invasion and migration ability of colorectal cancer cells were decreased significantly after LINC01123 knockdown, and it may inhibit its expression by interacted with SRSF7, thereby promoting colorectal cancer progression. CONCLUSIONS: LINC01123 can promote the proliferation, invasion and migration of colorectal cancer cells by regulating SRSF7, suggesting that it may be an important regulator of colorectal cancer progression.

Suppression of long intergenic non-protein coding RNA 1123 constrains lower extremity deep vein thrombosis via microRNA-125a-3p to target interleukin 1 receptor type 1.

Lower extremity deep vein thrombosis (LEDVT) is a disorder of venous return caused by abnormal blood clotting. LEDVT can obstruct the lumen and is the third most common vascular disease after cerebrovascular disease and coronary artery disease. LncRNAs are associated with thrombosis and potentially affect the pathogenesis of DVT. However, no studies have reported the effect of LINC01123 on LEDVT. The aim of this study was to investigate the effect of LINC01123 on LEDVT in rats via the miR-125a-3p/interleukin 1 receptor type 1 (IL1R1) axis. Lentiviral vectors that altering LINC01123, miR-125a-3p and IL1R1 expression were pre-injected into the tail vein of rats, and an LEDVT model was established 1 day later. Detection of LINC01123, miR-125a-3p and IL1R1 expression was performed. Inflammatory factors in femoral venous blood, the length and weight of the thrombus, the histomorphological changes were determined in the rat model. The targeting relation of miR-125a-3p with LINC01123 or IL1R1 was verified. The results presented that LEDVT rats expressed high LINC01123 and IL1R1 and low miR-125a-3p expression levels. After silencing LINC01123 or elevating miR-125a-3p, the rate of thrombosis, length and weight of thrombus, and levels of inflammatory factors were reduced. The targeting relation was presented between miR-125a-3p with LINC01123 or IL1R1. Elevating IL1R1 was available to turn around the action of silence of LINC01123 on LEDVT rats. All in all, suppression of LINC01123 restrains LEDVT via miR-125a-3p to target IL1R1.

LINC01123 promotes cell proliferation and migration via regulating miR-1277-5p/KLF5 axis in ox-LDL-induced vascular smooth muscle cells.

The pathophysiological mechanism of carotid atherosclerosis (CAS) involves endothelial cell dysfunction, vascular smooth muscle cells (VSMCs), and macrophage activation, which ultimately leads to fibrosis of the vessel wall. lncRNA works weightily in the formation of CAS, but the function and mechanism of lncRNA LINC01123 in stable plaque formation are still equivocal. We collected blood samples from 35 CAS patients as well as 33 healthy volunteers. VSMCs treated with oxidized low-density lipoprotein (ox-LDL) were utilized as the CAS cell models. We applied qRT-PCR for detecting LINC01123, miR-1277-5p and KLF5 mRNA expression, CCK-8 method and BrdU test for determining cell proliferation, Transwell test for measuring cell migration, as well as Western blot for assaying KLF5 protein expression. Dual-luciferase reporter experiment was adopted for assessing the interaction between LINC01123 and miR-1277-5p, as well as KLF5 and miR-1277-5p. LINC01123 and KLF5 expression were dramatically up-regulated, while miR-1277-5p expression was down-regulated in CAS patients and ox-LDL-induced CAS cell models. Overexpressed LINC01123 notedly promoted VSMCs migration and proliferation. LINC01123 knockdown repressed cell proliferation and migration. Also, LINC01123 targeted miR-1277-5p and down-regulated its expression, while miR-1277-5p could negatively regulate KLF5 expression. LINC01123 is highly expressed in CAS patients, and promotes cell proliferation and migration via regulating miR-1277-5p/KLF5 axis in ox-LDL-induced VSMCs. It might be involved in the fibrous plaque formation.

LINC01123 Promotes the Progression of Colorectal Cancer via miR-625-5p/LASP1 Axis.

Background: Evidence from previous investigations points to a rising trend in the incidence of colorectal cancer (CRC) worldwide. The mortality resulting from this cancer is high. Unlike nonsmall cell lung cancer for which LINC01123 has been investigated, there are few reports on how this long noncoding RNA (lncRNA) regulates CRC. Materials and Methods: The authors evaluated the expression of LINC01123 in CRC tissues by quantitative real-time polymerase chain reaction. Its impact on cancer cell behavior was analyzed with cell counting kit-8 (CCK-8), colony formation, and Transwell invasion assays. To establish the mechanisms of LINC01123 in CRC they carried out RIP and luciferase reporter assays. Results: The results show that LINC01123 expression is abnormally elevated in CRC tissues and cell lines. High LINC01123 expression closely correlates with poor prognosis, advanced TNM stage, and lymph-node metastasis. The authors also show that knockdown of LINC01123 inhibits proliferation and invasion in CRC cells. In mechanism, it is revealed that LINC01123 may function as competitive endogenous RNA (ceRNA) against miR-625-5p to promote LIM and SH3 protein 1 (LASP1) expression. Conclusions: The data indicate that high LINC01123 exerts its oncogenic roles by regulating the miR-625-5p/LASP1 axis in CRC progression.

LINC01123 facilitates proliferation, invasion and chemoresistance of colon cancer cells.

Colon cancer is one of the major causes of cancer-related deaths worldwide. Long non-coding RNA (lncRNA) LINC01123 has been suggested to act as an oncogene in non-small cell lung cancer and a prognostic signature in head and neck squamous cell carcinoma. However, its role in colon cancer remains obscure. From TCGA database, LINC01123 was observed to be up-regulated in colon adenocarcinoma (COAD). Subsequently, the up-regulated LINC01123 was also detected in colon cancer cells. Functionally, LINC01123 could enhance cell proliferation, migration, invasion and angiogenesis. Moreover, the chemoresistance of colon cancer cells was verified to be promoted by LINC01123. Afterward, LINC01123 was found to bind with Ago2 and miR-34c-5p. Besides, miR-34c-5p was confirmed to inhibit the cellular process and chemoresistance of colon cancer cells. Then, VEGFA was disclosed to coexist with LINC01123 and miR-34c-5p in RNA-induced silencing complex. And TCGA database suggested that its expression was correlated with different stages of COAD. Moreover, it was uncovered that VEGFA could bind with miR-34c-5p and its expression positively correlated with LINC01123 expression. Finally, LINC01123 was proofed to regulate colon cancer progression and cells chemoresistance via VEGFA. In conclusion, LINC01123/miR-34c-5p/VEGFA axis promotes colon cancer malignancy and cells chemoresistance.

STAT1-induced upregulation of lncRNA LINC01123 predicts poor prognosis and promotes the progression of endometrial cancer through miR-516b/KIF4A.

Long non-coding RNAs (lncRNAs) have been proposed as suppressors or promoters in many tumor processes. LncRNA LINC01123 (LINC01123) was a newly identified lncRNA which was firstly functionally analyzed in lung cancer. However, its expression and function in other tumor types were rarely reported. In this study, we firstly confirmed that LINC01123 was highly expressed in both endometrial cancer (EC) tissues and cell lines using bioinformatics analysis and RT-CPR. Then, we preliminarily analyzed the mechanisms involved in overexpression of LINC01123 in EC, finding that STAT1 could bind directly to the LINC01123 promoter region and activate its transcription. Clinical research with 106 patients indicated that high expression of LINC01123 was associated with advanced clinical progression and poor clinical outcome of EC patients. Functionally, knockdown of LINC01123 suppressed the proliferation, migration and invasion of EC cells, and promoted apoptosis. Mechanistically, we observed that LINC01123 may act as an endogenous sponge by competing for miR-516b, thereby regulating KIF4A. Overall, our study revealed a novel LINC01123/miR-516b/KIF4A pathway regulatory axis in EC pathogenesis. LINC01123 may be a novel prognostic biomarker and therapeutic target in EC.Abbreviations: EC: Endometrial cancer; LncRNA: Long non-coding RNA; EMT: epithelial-mesenchymal transition; miRNA: microRNA; qRT-PCR: Quantitative real-time polymerase chain reaction; SPSS: Statistical Package for Social Sciences; Chip: chromatin-immunoprecipitation, TCGA: The Cancer Genome Atlas; CCK-8: Cell Counting Kit-8; KIF4A: Chromosome-associated kinesin KIF4A.

Long noncoding RNA LINC01123 promotes the proliferation and invasion of hepatocellular carcinoma cells by modulating the miR-34a-5p/TUFT1 axis.

Hepatocellular carcinoma (HCC), one of the main causes of cancer-related deaths globally, is characterized by rapid growth and high invasiveness. Accumulating evidence demonstrates that long noncoding RNAs (lncRNAs) play critical roles in the growth and metastasis of HCC. Recently, lncRNA LINC01123 has been found to contribute to cell proliferation and aerobic glycolysis in lung cancer. However, the function of LINC01123 in HCC, as well as the underlying mechanism of its action, remain unclear. Here, we found that the expression of LINC01123 was clearly upregulated in HCC tissues compared to nontumor tissues. Furthermore, expression of LINC01123 in HCC cells was significantly higher than in LO2 cells. Importantly, the upregulated level of LINC01123 was related to unfavorable clinical features and poor prognosis of HCC. Next, we demonstrated that LINC01123 knockdown suppressed the proliferation, migration and invasion of HCC cells in vitro. Depletion of LINC01123 inhibited HCC xenograft growth in vivo. Conversely, ectopic expression of LINC01123 facilitated HCC cell proliferation and invasion. Mechanistically, LINC01123 acted as a molecular sponge for miR-34a-5p in HCC cells. Tuftelin1 (TUFT1) was identified as the target gene of miR-34a-5p. LINC01123 positively regulated TUFT1 level by targeting of miR-34a-5p in HCC cells. Notably, TUFT1 restoration can abolish miR-34a-5p-induced inhibitory effects on HCC cell proliferation, migration and invasion. In conclusion, LINC01123 was overexpressed in HCC and accelerated cancer cell proliferation and invasion by regulating the miR-34a-5p/TUFT1 axis.

LINC01123, a c-Myc-activated long non-coding RNA, promotes proliferation and aerobic glycolysis of non-small cell lung cancer through miR-199a-5p/c-Myc axis.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been associated with non-small cell lung cancer (NSCLC), but the underlying molecular mechanisms of their specific roles in mediating aerobic glycolysis have been poorly explored. METHODS: Next-generation RNA sequencing assay was performed to identify the differentially expressed RNAs between NSCLC tissues with high 18F-fluorodeoxyglucose (FDG) uptake and their adjacent normal lung tissues. LINC01123 expression in NSCLC tissues was measured by real-time PCR and in situ hybridization (ISH) assay. The biological role of LINC01123 in cell growth and aerobic glycolysis capability was determined by performing functional experiments in vitro and in vivo. Further, the transcription of LINC01123 was explored by bioinformatics analysis, dual-luciferase reporter assay, and chromatin immunoprecipitation (ChIP) assay. RNA immunoprecipitation (RIP) and luciferase analyses were used to confirm the predicted competitive endogenous RNA (ceRNA) mechanisms between LINC01123 and c-Myc. RESULTS: Three hundred sixty-four differentially expressed genes were identified in RNA-seq assay, and LINC01123 was one of the most overexpressed lncRNAs. Further validation in expanded NSCLC cohorts confirmed that LINC01123 was upregulated in 92 paired NSCLC tissues and associated with poor survival. Functional assays showed that LINC01123 promoted NSCLC cell proliferation and aerobic glycolysis. Mechanistic investigations revealed that LINC01123 was a direct transcriptional target of c-Myc. Meanwhile, LINC01123 increased c-Myc mRNA expression by sponging miR-199a-5p. In addition, rescue experiments showed that LINC01123 functioned as an oncogene depending on miR-199a-5p and c-Myc. CONCLUSION: Since LINC01123 is upregulated in NSCLC, correlates with prognosis, and controls proliferation and aerobic glycolysis by a positive feedback loop with c-Myc, it is expected to be a potential biomarker and therapeutic target for NSCLC.