ERß-activated LINC01018 promotes endometriosis development by regulating the CDC25C/CDK1/CyclinB1 pathway.

Endometriosis refers to as an estrogen-dependent disease. Estrogen receptor ß (ERß), the main estrogen receptor subtype which is encoded by the estrogen receptor 2 (ESR2) gene, can mediate the action of estrogen in endometriosis. Although selective estrogen receptor modulators can target the ERß, they are not specific due to the wide distribution of ERß. Recently, long noncoding RNAs have been implicated in endometriosis. Therefore, we aim to explore and validate the downstream regulatory mechanism of ERß, and to investigate the potential role of long intergenic noncoding RNA 1018 (LINC01018) as a nonhormonal treatment for endometriosis. Our study demonstrates that the expression levels of ESR2 and LINC01018 are increased in ectopic endometrial tissues and reveals a significant positive correlation between the ESR2 and LINC01018 expression. Mechanistically, ERß directly binds to an estrogen response element located in the LINC01018 promoter region and activates LINC01018 transcription. Functionally, ERß can regulate the CDC25C/CDK1/CyclinB1 pathway and promote ectopic endometrial stromal cell proliferation via LINC01018 in vitro. Consistent with these findings, the knockdown of LINC01018 inhibits endometriotic lesion proliferation in vivo. In summary, our study demonstrates that the ERß/LINC01018/CDC25C/CDK1/CyclinB1 signaling axis regulates endometriosis progression.

Prognostic value of lncRNA LINC01018 in prostate cancer by regulating miR-182-5p (The role of LINC01018 in prostate cancer).

LncRNAs are abnormally expressed in a variety of cancers and play unique roles in therapy. Based on this, the prognostic value of lncRNA LINC01018 in prostate cancer was discussed in this study. LINC01018 was underexpressed in prostate cancer tissues and cells, while miR-182-5p was elevated (***p < 0.001). Overexpression of LINC01018 may inhibit the progression of prostate cancer by targeting miR-182-5p. This study revealed that upregulated LINC01018 may prolong the overall survival of patients with prostate cancer (log-rank p = 0.042), and LINC01018 may become a prognostic biomarker for patients with prostate cancer, which brings a new direction for the treatment of patients.

LncRNA LINC01018/miR-942-5p/KNG1 axis regulates the malignant development of glioma in vitro and in vivo.

AIMS: Since the inhibitory effect of KNG1 on glioma has been proved, this study further explores the regulation of the lncRNA/miRNA axis on KNG1 in glioma. METHODS: The miRNAs that target KNG1 and the lncRNA that targets miR-942-5p were predicted by bioinformatics analysis and verified by experiments. The correlations between miR-942-5p and the survival of patients and between KNG1 and miR-942-5p were analyzed. After transfection, cell migration, invasion, proliferation, and cell cycle were detected through wound healing, Transwell, colony formation, and flow cytometry assays. A mouse subcutaneous xenotransplanted tumor model was established. The expressions of miR-942-5p, KNG1, LINC01018, and related genes were evaluated by quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR), Western blot, or immunohistochemistry. RESULTS: MiR-942-5p targeted KNG1, and LINC01018 sponged miR-942-5p. The high survival rate of patients was related to low miR-942-5p level. MiR-942-5p was highly expressed, whereas KNG1 was lowly expressed in glioma. MiR-942-5p was negatively correlated with KNG1. Silent LINC01018 or KNG1 and miR-942-5p mimic enhanced the migration, invasion, and proliferation of glioma cells, and regulated the expressions of metastasis-related and proliferation-related genes. LINC01018 knockdown and miR-942-5p mimic promoted glioma tumor growth in mice. The levels of miR-942-5p and KNG1 were decreased by LINC01018 knockdown, and LINC01018 expression was suppressed by miR-942-5p mimic. MiR-942-5p inhibitor, KNG1, and LINC01018 had the opposite effect to miR-942-5p mimic. CONCLUSION: LINC01018/miR-942-5p/KNG1 pathway regulates the development of glioma cells in vitro and in vivo.

Long non-coding RNA LINC01018 inhibits human glioma cell proliferation and metastasis by directly targeting miRNA-182-5p.

AIM: Accumulating evidence suggests that lncRNAs are potential biomarkers and key regulators of tumor development and progression. However, the precise function of most lncRNAs in glioma remains unknown. In this study, we explored the role of long intergenic non-protein coding RNA 1018 (LINC01018) in human glioma. METHODS: Expression levels of LINC01018 and miR-182-5p in clinical glioma tissues and cell lines were detected by quantitative real-time PCR (qRT-PCR). Cell proliferation, migration, and invasion were determined by Cell Counting Kit-8 (CCK-8) assay and Transwell assay. Epithelial-mesenchymal transition (EMT) related proteins were measured by Western blotting. Direct relationship between LINC01018 and miR-182-5p was tested by dual-luciferase reporter assay, RNA immunoprecipitation assay (RIP), and rescue assays. Lastly, bioinformatics analyses were conducted to predict the downstream factors of LINC01018/miR-182-5p axis in glioma. RESULTS: LINC01018 was significantly down-regulated in glioma tissues and cell lines. Overexpression of LINC01018 dramatically inhibited cell proliferation, migration, and invasion and reverse EMT process in glioma. LINC01018 directly target to miR-182-5p. Forced up-regulation of miR-182-5p reversed the inhibitory effects on proliferative and metastatic abilities of glioma cells with LINC01018 overexpression. Lastly, the bioinformatics analyses revealed that LINC01018/miR-182-5p axis mediated a cluster of downstream genes (ADRA2C, RAB6B, RAB27B, RAPGEF5, STEAP2, TAGLN3, and UNC13C), which were potential key factors in the development of glioma. CONCLUSION: LINC01018 inhibits cell proliferation and metastasis in human glioma by targeting miR-182-5p, and should be considered as a potential therapeutic target in this cancer.

Long non-coding RNA LINC01018 inhibits the progression of acute myeloid leukemia by targeting miR-499a-5p to regulate PDCD4.

Acute myeloid leukemia (AML) is a highly heterogeneous disease with a very high mortality rate. In recent years, an increasing number of studies have proven that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) may serve as useful biomarkers in various cancer types. However, the mechanism of LINC01018 and miR-499a-5p in AML requires further investigation. The mRNA expression of LINC01018, miR-499a-5p and PDCD4 in AML tissues and cells was detected using reverse transcription-quantitative polymerase chain reaction. Cell proliferation was measured using Cell Counting kit-8 and EdU assays. Cell apoptosis was monitored via a TUNEL staining assay. Protein expression of PDCD4, Bax and Bcl-2 was measured using western blot analysis. The interaction between PDCD4 and LINC01018 or miR-499a-5p was verified by RNA pull-down, RIP and dual-luciferase reporter assays. LINC01018 and PDCD4 were downregulated in AML, while miR-499a-5p was upregulated. LINC01018-overexpression suppressed AML cell proliferation and induced AML cell apoptosis, while miR-499a-5p transfection reversed these effects. LINC01018 acted as a sponge of miR-499a-5p, and PDCD4 was demonstrated to be targeted by miR-499a-5p. Knockdown of miR-499a-5p suppressed AML cell proliferation and promoted AML cell apoptosis, but silencing PDCD4 abolished this effect. LINC01018 inhibited AML cell growth by modulating PDCD4 through suppression of miR-499a-5p, providing a feasible theoretical basis for the treatment of AML.

LINC01018 confers a novel tumor suppressor role in hepatocellular carcinoma through sponging microRNA-182-5p.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality. Emerging evidence has demonstrated that some long noncoding RNAs (lncRNAs) are involved in the development and progression of HCC. Herein, the current study aimed to explore the potential mechanism of LINC01018 in regulating the progression of HCC. Initially, the expression of LINC01018, microRNA-182-5p (miR-182-5p), and forkhead box protein O1 (FOXO1) was quantified in 72 paired HCC and adjacent normal tissue samples as well as HCC cells, followed by identification of the interaction among them. To define the contributory role of LINC01018 in the progression of HCC, the expression of LINC01018, miR-182-5p, or FOXO1 was altered in HCC cells, followed by evaluation of cell proliferation, cell cycle distribution, and cell apoptosis. Finally, in vivo tests were performed to further verify the role of LINC01018 in HCC. It was observed that LINC01018 and FOXO1 were poorly expressed but miR-182-5p was highly expressed in HCC tissues and cells. The upregulation of LINC01018 was shown to decrease proliferation while promoting apoptosis of HCC cells. LINC01018 acted as a sponge of miR-182-5p, which targeted FOXO1. Last, mice injected with Hep3B overexpressing FOXO1 displayed suppressed xenograft tumor formation. Collectively, overexpression of LINC01018 represses proliferation and promotes apoptosis of HCC cells via upregulation of FOXO1 by sponging miR-182-5p, which highlights overexpression of LINC01018 as a candidate suppressor of HCC.NEW & NOTEWORTHY This study provides evidence for understanding the molecular mechanism involved in the progression of hepatocellular carcinoma and identifies a novel network of LINC01018/miR-182-5p/FOXO1. We also conducted in vivo experiments in nude mice to validate the anti-tumor effect of LINC01018.