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Background: Luminal A and B subtypes of breast cancer (BC) comprises up to 70% of all BC patients. LncRNAs can affect many biological and pathological processes, and dysregulation of them is related to human cancers. The potential role of lncRNA LINC00968 in luminal BC is still unclear. Materials and methods: We analyzed the LINC00968 expression across 44 paired luminal BC tissues from the TCGA-BRCA RNA sequencing dataset. Besides, we used the GEPIA2 web server and GENEVESTIGATOR software, as well. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) assay was performed to confirm the LINC00968 expression in 71 paired luminal BC tissues and two luminal A cell lines (MCF7 and T47D). Moreover, to better understanding the potential role of LINC00968 in luminal BC, computational data analyses including co-expression analysis, functional annotation analysis, and genetic alteration analysis have been done. Results: The results of data analyses retrieved from BRCA dataset and databases revealed the significant downregulation of LINC00968 in luminal A and B BC. Also, the results of qRT-PCR in luminal BC tissues and cell lines confirmed the earlier data. LINC00968 expression was negatively associated with tumor stage and lymph node metastasis. Additionally, functional annotation analyses revealed that LINC00968 might be involved in vascular development and angiogenesis, extracellular matrix organization, and cell motility and migration. LINC00968 might play role in some cancer-related signaling pathways. Conclusion: Our study found that downregulation of LINC00968 might promote tumorigenesis, invasion, and metastasis of luminal BC.

As a major cause of mortality, cardiovascular disease is associated with obesity and diabetes. However, the molecular mechanism by which diabetes-obesity causes cardiovascular complications is largely unknown. In this study, the crosstalk mediated by 3T3-L1 preadipocytes and mouse retina microvascular endothelial cells (mRMECs) was determined after co-culturing performed with a Transwell system or measuring exosome uptake by mRMECs. CCK-8 assays, EdU incorporation assays, TUNEL staining, and ELISAs were used to evaluate the functions of mRMECs. Related protein markers were analyzed by western blotting. Our results showed that LINC00968 levels were significantly elevated in the exosomes derived from H-Glu-induced 3T3-L1 preadipocytes. Both H-Glu treatment and co-culture with 3T3-L1 cells damaged mRMECs, as indicated by lower rates of proliferation and higher rates of apoptosis and cell adhesion molecule expression, as well as by induced inflammation and oxidative stress, which were enhanced by combined H-Glu and co-culture treatment. Furthermore, H-Glu and co-culture treatment increased LINC00968 expression in mRMECs, and the exosomes collected from 3T3-L1 cells had a similar effect. Functionally, LINC00968 inhibition protected mRMECs against the effects of H-Glu and co-culture treatment, while LINC00968 played the opposite role. LINC00968 was found to target miR-361–5p, and TRAF3 was identified as a target gene of miR-361–5p. Finally, miR-361–5p overexpression alleviated the effects of LINC00968 on H-Glu-induced mRMEC dysfunction in vitro. In conclusion, our results indicated that in an H-glu environment, adipocyte exosomes damage microvascular endothelial cells via a LINC00968/miR-361–5p/TRAF3 signaling pathway, which could possibly serve as a target for treating diabetes-obesity-triggered microvascular complications. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LUAD) is a high aggressive human cancer which usually diagnosed at advanced stages. Accumulating evidences indicate that long noncoding RNAs (lncRNAs) are crucial participants in LUAD progression. In the present study, we found that lncRNA LINC00968 was significantly down-regulated in LUAD tissues and cell lines. LINC00968 level was positively correlated to survival rate, and negatively correlated to tumor node metastasis (TNM) stage, tumor size and lymph node metastasis of LUAD patients. We over-expressed LINC00968 in LUAD cells using lentivirus, inhibited proliferation and cell cycle arrest at G1 phase were detected. LINC00968 over-expression also suppressed migration, invasion and epithelial mesenchymal transition. We further validated that LINC00968 localized in cytoplasm and acted as an upstream regulator of microRNA miR-22-5p, which was up-regulated in LUAD tissues and cell lines. Besides, elevated miR-22-5p expression abolished the effect of LINC00968 over-expression on LUAD progression including in vivo tumor growth. In addition, we first validated that cell division cycle 14A (CDC14A), which was down-regulated in LUAD tissues, was a downstream target of miR-22-5p. We over-expressed CDC14A in LUAD cells and miR-22-5p induced LUAD progression was partially reversed. In conclusion, our study demonstrated that LINC00968 inhibited proliferation, migration and invasion of LUAD by sponging miR-22-5p and further restoring CDC14A. This novel regulatory axis might provide us with promising diagnostic and therapeutic target in LUAD treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Breast cancer is one the most common cancers, making it the second leading cause of cancer-related death among women. Long non-coding RNAs (lncRNAs), with tightly regulated expression patterns, also serve as tumor suppressor during tumorigenesis. The present study aimed to elucidate the role of LINC00968 in breast cancer via WNT2-mediated Wnt2/β-catenin signaling pathway. Methods Breast cancer chip GSE26910 was utilized to identify differential expression in LINC00968 and WNT2. The possible relationship among LINC00968, transcriptional repressor HEY and WNT2 was analyzed and then verified. Effects of LINC00968 on activation of the Wnt2/β-catenin signaling pathway was also tested. Drug resistance, colony formation, cell migration, invasion ability and cell apoptosis after transfection were also determined. Furthermore, tumor xenograft in nude mice was performed to test tumor growth and weight in vivo. Results WNT2 expression exhibited at a high level, whereas LINC00968 at a low expression in breast cancer which was also associated with poor prognosis in patients. LINC00968 targeted and negatively regulated WNT2 potentially via HEY1. Either overexpressed LINC00968 or silenced inhibited activation of the Wnt2/β-catenin signaling pathway, thereby reducing drug resistance, decreasing colony formation ability, as well as suppressing migration and invasion abilities of breast cancer cells in addition to inducing apoptosis. Lastly, in vivo experiment suggested that LINC00968 overexpression also suppressed transplanted tumor growth in nude mice. Conclusion Collectively, overexpressed LINC00968 contributes to reduced drug resistance in breast cancer cells by inhibiting the activation of the Wnt2/β-catenin signaling pathway through silencing WNT2. This study offers a new target for the development of breast cancer treatment.

OBJECTIVE: The aim of this study was to clarify the potential role of LINC00968 in the progression of epithelial ovarian cancer (EOC) and the underlying mechanism. PATIENTS AND METHODS: The relative expression level of LINC00968 in EOC tissues (n=40) and normal ovarian tissues (n=40) was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). LINC00968 expression in human-derived ovarian cancer cell lines was examined by qRT-PCR as well. After transfection of LINC00968 small-interfering RNA (siRNA) in ovarian cancer cells, cell cycle progression and cell proliferation were evaluated through flow cytometry, Cell Counting Kit-8 (CCK-8) and colony formation assay, respectively. Tumor xenograft was conducted in nude mice to elucidate the function of LINC00968 in EOC tumorigenesis in vivo. Furthermore, the relative expression levels of cell cycle factors and protein kinase B/extracellular-signal-regulated kinase (AKT/ERK) in ovarian cancer cells influenced by LINC00968 were detected by Western blot. RESULTS: LINC00968 was significantly up-regulated in EOC tissues when compared with normal control tissues. Meanwhile, LINC00968 expression was positively correlated with the prognosis of EOC. Transfection of LINC00968 siRNA in HEY and HO8910 cells markedly attenuated proliferative ability and arrested cell cycle in the G1 phase. Knockdown of LINC00968 remarkably suppressed tumor growth of EOC in nude mice. The silence of LINC00968 significantly downregulated Cyclin D, Cyclin E and CDK4, whereas upregulated p16 and p21. In addition, AKT and ERK pathways were inhibited by knockdown of LINC00968 in ovarian cancer cells. CONCLUSIONS: LINC00968 expression is markedly upregulated in EOC. Meanwhile, it arrests the cell cycle in the G1 phase by inhibiting the ERK and AKT pathways, thus accelerating EOC progression. [ABSTRACT FROM AUTHOR]

Osteosarcoma is recognized as a malignant tumor in the skeletal system. Long non‐coding RNAs (lncRNAs) have been exhibited to play crucial roles in osteosarcoma development. Our current study focused on the biological effects and mechanism of LINC00968 in osteosarcoma pathogenesis. We observed that LINC00968 was dramatically elevated in osteosarcoma cells including U2OS, MG63, Saos‐2, SW1353, and 143‐B cells compared to human osteoblast cell line hFOB. Silence of LINC00968 inhibited osteosarcoma cell growth and proliferation in vitro. Reversely, overexpression of LINC00968 promoted osteosarcoma cell survival and cell colony formation ability in Saos‐2 and 143‐B cells. In addition, LINC00968 was able to induce osteosarcoma cell migration and invasion through up‐regulating MMP‐2 and MMP‐9 protein levels. The phosphoinosmde‐3‐kinase/Protein Kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway has been reported to participate in several cancer types. Here, in our study, we found that PI3K/AKT/mTOR pathway was involved in osteosarcoma progression. Knockdown of LINC00968 inactivated PI3K/AKT/mTOR signaling pathway in vitro. Subsequently, in vivo tumor xenografts were established using 143‐B cells to investigate whether LINC00968 can induce osteosarcoma development in vivo. Consistently, it was indicated that inhibition of LINC00968 significantly inhibited osteosarcoma progression in vivo. Taken these together, in our research, LINC00968 could be provided as a novel prognostic biomarker and therapeutic target in osteosarcoma diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Abstract Emerging evidence have indicated the vital roles of long noncoding RNAs (lncRNAs) in the pathophysiological process of diabetic nephropathy. However, the deepgoing mechanism that lncRNAs regulate the diabetic nephropathy pathogenesis is still ambiguous. In present study, we found that lncRNA LINC00968 expression was high-expressed in the diabetic db/db mouse tissue and high-glucose induced mesangial cells. Functional experiments indicated that LINC00968 silencing by siRNAs significantly inhibited the proliferation and cycle progression, and decreased the extracellular matrix (ECM) proteins (fibronectin, collagen IV) expression in the high glucose induced of mesangial cells. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assay revealed that LINC00968 recruit EZH2 to the promoter of p21 to inhibit its expression. In summary, our results support the conclusion that lncRNA LINC00968 accelerates the proliferation and fibrosis of mesangial cells by epigenetically repressing p21 via recruiting EZH2, providing a novel insight for the diabetic nephropathy pathogenesis. Highlights • LncRNA LINC00968 was high-expressed in the diabetic db/db mouse tissue and high-glucose induced mesangial cells. • LINC00968 silencing inhibited the proliferation and cycle progression. • LINC00968 silencing decreased the extracellular matrix (ECM) proteins (fibronectin, collagen IV) expression. • RIP and ChIP assay revealed that LINC00968 recruit EZH2 to the promoter of p21 to inhibit its expression. [ABSTRACT FROM AUTHOR]

Long non‑coding RNAs (lncRNAs) have been demonstrated to mediate carcinogenesis in various types of cancer. However, the regulatory role of lncRNA LINC00968 in lung adenocarcinoma remains unclear. The microRNA (miRNA) expression in LINC00968‑overexpressing human lung adenocarcinoma A549 cells was detected using miRNA microarray analysis. miR‑9‑3p was selected for further analysis, and its expression was verified in the Gene Expression Omnibus (GEO) database. In addition, the regulatory axis of LINC00968 was validated using The Cancer Genome Atlas (TCGA) database. Results of the GEO database indicated miR‑9‑3p expression in lung adenocarcinoma was significantly higher compared with normal tissues. Functional enrichment analyses of the target genes of miR‑9‑3p indicated protein binding and the AMP‑activated protein kinase pathway were the most enriched Gene Ontology and KEGG terms, respectively. Combining target genes with the correlated genes of LINC00968 and miR‑9‑3p, 120 objective genes were obtained, which were used to construct a protein‑protein interaction (PPI) network. Cyclin A2 (CCNA2) was identified to have a vital role in the PPI network. Significant correlations were detected between LINC00968, miR‑9‑3p and CCNA2 in lung adenocarcinoma. The LINC00968/miR‑9‑3p/CCNA2 regulatory axis provides a new foundation for further evaluating the regulatory mechanisms of LINC00968 in lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) have played critical roles in a variety of cancers, including non-small cell lung cancer (N SCLC). In our study,wefocused on the biological function and clinical significance of lncRNA LINC00968 in NSCLC. It was indicated that LINC00968 was significantly increased in LUAD tissues, LUSC tissues and NSCLC cells compared to their corresponding controls. Inhibition of LINC00968 was able to repress NSCLC growth, migration, and invasion in vitro while upregulation of LINC00968 reversed this process. Additionally, downregulation of LINC00968 induced apoptosis capacity of A549 cell. Apoptosis-related proteins BCL-2 were decreased and BAX was increased by knockdown of LINC00968, respectively. Meanwhile we observed that Wnt signaling pathway was involved in the LINC00968-induced NSCLC progression. Finally, in vivo tumor xenografts were established using A549 cells to detect the function of LINC00968 in NSCLC tumorigenesis. Silencing LINC00968 greatly inhibited NSCLC tumor progression, which was consistent with the in vitro tests. In conclusion, we have uncovered that LINC00968 could be regarded as a novel prognostic biomarker and therapeutic target in NSCLC diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is one the most common cancers, making it the second leading cause of cancer-related death among women. Long non-coding RNAs (lncRNAs), with tightly regulated expression patterns, also serve as tumor suppressor during tumorigenesis. The present study aimed to elucidate the role of LINC00968 in breast cancer via WNT2-mediated Wnt2/β-catenin signaling pathway. Methods: Breast cancer chip GSE26910 was utilized to identify differential expression in LINC00968 and WNT2. The possible relationship among LINC00968, transcriptional repressor HEY and WNT2 was analyzed and then verified. Effects of LINC00968 on activation of the Wnt2/β-catenin signaling pathway was also tested. Drug resistance, colony formation, cell migration, invasion ability and cell apoptosis after transfection were also determined. Furthermore, tumor xenograft in nude mice was performed to test tumor growth and weight in vivo. Results: WNT2 expression exhibited at a high level, whereas LINC00968 at a low expression in breast cancer which was also associated with poor prognosis in patients. LINC00968 targeted and negatively regulated WNT2 potentially via HEY1. Either overexpressed LINC00968 or silenced inhibited activation of the Wnt2/β-catenin signaling pathway, thereby reducing drug resistance, decreasing colony formation ability, as well as suppressing migration and invasion abilities of breast cancer cells in addition to inducing apoptosis. Lastly, in vivo experiment suggested that LINC00968 overexpression also suppressed transplanted tumor growth in nude mice. Conclusion: Collectively, overexpressed LINC00968 contributes to reduced drug resistance in breast cancer cells by inhibiting the activation of the Wnt2/β-catenin signaling pathway through silencing WNT2. This study offers a new target for the development of breast cancer treatment. [ABSTRACT FROM AUTHOR]