The long intergenic non-coding RNA LINC01140 modulates gastric cancer phenotypes and cancer cell lines aggressiveness.

BACKGROUND: Long-intergenic non-protein coding gene 01140 (LINC01140) a long non-coding RNA is highly expressed in various cancers. However, its biological functions in gastric cancer progression is still unknown. METHOD: To elucidate LINC01140 function, 70 GC tumor samples and 30 normal gastric tissues were collected. LINC01140 expression level were determined by qRT-PCR analysis and correlated with different clinico-pathological parameters. Then we tried to see the impact of LINC01140 on gastric cell line aggressiveness by knocking down the target gene and performing cell viability assay, migration assay and invasive capacity of the cell lines along with immunoblotting to check several protein levels. RESULT: LINC01140 RNA is found to be positively correlated with FGF9 and significantly up regulated in GC tissues. LINC01140 knockdown inhibited the viability, migratory capacity and invasive capacity of AGS cells. LINC01140 targets miR-140-5p, while miR-140-5p targeted FGF9 to form lncRNA-miRNA-mRNA axis. The affect of miR-140-5p inhibition on gastric cancer cell aggressiveness were opposite to those of LINC01140 or FGF9 knockdown. Additionally, inhibition partially reversed the effects of LINC01140 knockdown on FGF9 protein levels, gastric cancer cell phenotypes. CONCLUSION: LINC01140, miR-140-5p and FGF9 form a lncRNA-miRNA-mRNA axis that modulates the gastric cancer phenotypes and in turn affects gastric cancer cell aggressiveness.

LINC01140 Hinders the Development of Breast Cancer Through Targeting miR-200b-3p to Downregulate DMD.

Long non-coding RNAs (lncRNAs) are frequently reported to be involved in breast cancer (BC) oncogenicity. The goal of this study was to probe lncRNA LINC01140's role and action mechanism in BC. Relative LINC01140, miR-200b-3p, and dystrophin (DMD) levels were determined using quantitative real-time polymerase chain reaction (qRT-PCR). DMD protein levels in BC cells were quantified using Western blotting, and the targeting relationships were validated by luciferase reporter assays and RNA immunoprecipitation experiments. The proliferative potential of the cells was evaluated using CCK-8 and colony formation tests, while the migratory and invasive abilities of the cells were assessed using scratch and transwell assays. Apoptosis was assessed by flow cytometry. Nude mouse models have been established to allow the examination of tumor growth in vivo. Pronounced downregulation of LINC01140 and DMD, as well as upregulation of miR-200b-3p, was observed in BC. LINC01140 binds directly to miR-200b-3p to downregulate DMD expression. Ectopic LINC01140 expression not only limited tumor growth in vivo but also diminished the proliferation, migration, and invasion abilities of BC cells in vitro, however, it induced apoptosis in BC cells. Elevated miR-200b-3p expression stimulated the tumorigenic potential of BC cells and attenuated the suppressive effect of LINC01140 or DMD overexpression on BC cell malignancy, whereas DMD overexpression restricted the tumorigenic potential of BC cells. Overall, LINC01140 prevents BC development via the miR-200b-3p-DMD axis. These findings support the latent potential and usefulness of the LINC01140-miR-200b-3p-DMD network as a target for BC therapy.

LINC01140 regulates osteosarcoma proliferation and invasion by targeting the miR-139-5p/HOXA9 axis.

Osteosarcoma is one of the commonest metastatic tumor in children and teenagers, and has a hopeless, prognosis. Long non-coding RNA (lncRNA) acts momentous roles as a regulator on the proliferation and migration of cancer. Here, we performed GEO database analysis and qPCR to identify differentially expressed lncRNAs in osteosarcoma cells. Knockdown of lncRNA LINC01140 was used to detect the effect of LINC01140 on the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of osteosarcoma cells. Bioinformatics analysis and qPCR identified the LINC01140/miR-139-5p/Homeobox A9 (HOXA9) regulatory axis. RNA immunoprecipitation assay, Dual-luciferase assay, and rescue experiments confirmed the interaction of LINC01140/miR-139-5p/HOXA9 in osteosarcoma. LINC01140 was overexpressed in osteosarcoma and knocking down LINC01140 restrained the proliferation and invasion of osteosarcoma cells and EMT. In Saos2 and MG63 cells, LINC01140 sponged miR-139-5p, and a miR-139-5p inhibitor overturned the suppression of LINC01140 knockdown on the proliferation and migration of osteosarcoma cells. Moreover, miR-139-5p depressed the invasion, proliferation, and EMT of osteosarcoma cells via targeting HOXA9. Our results indicate that LINC01140 downregulation inhibits the invasion, proliferation, and EMT in osteosarcoma cells through targeting the miR-139-5p/HOXA9 axis. Therefore, LINC01140 is a potential therapeutic target for osteosarcoma.

LncRNA LINC01140 Inhibits Glioma Cell Migration and Invasion via Modulation of miR-199a-3p/ZHX1 Axis.

PURPOSE: Glioma is an aggressive tumor from the nervous system, which causes more than 70% of primary malignant brain tumors. Considering its severe malignancy, there is an urgent need to investigate more practical markers to understand the pathogenesis of glioma, and potential treatment methods for glioma patients. In the paper, we are focused on examining the roles of LINC01140, miR-199a-3p, and ZHX1 in the progression of gliomas, as well as their inner associations and modulation mechanisms. METHODS: qRT-PCR was employed to examine the expression levels of LINC01140 and miR-199a-3p. We measured the expressions of ZHX1 via qRT-PCR and Western blotting. CCK8 assays, migration assays, and invasion assays were carried out to determine the cell viabilities and abilities of migration and invasion. We also conducted in vivo tumor growth experiments to investigate the roles of LINC01140 in glioma developments. RESULTS: The expressions of LINC01140 were promoted in glioma. Silencing LINC01140 could inhibit glioma cell viabilities, migration, and invasion. In our experiments, miR-199a-3p was inhibited in glioma. LINC01140 negatively regulated the expressions of miR-199a-3p in glioma. MiR-199a-3p could target ZHX1 to inhibit its expression in glioma cells. CONCLUSION: LINC01140 could promote glioma developments by modulating the miR-199a-3p/ZHX1 axis.

Downregulation of LINC01140 is associated with adverse features of breast cancer.

Breast cancer (BC) is one of the most dangerous malignant diseases among women. A growing amount of evidence has suggested that long non-coding RNAs participate in the development and progression of BC and may potentially serve as therapeutic targets or prognostic markers for the disease. A previous study demonstrated that long intergenic non-protein coding RNA 01140 (LINC01140) was prominently correlated with overall survival in patients with gastric cancer. However, the function of LINC01140 in BC has not yet been elucidated. Therefore, the present study aimed to investigate the roles and molecular mechanisms underlying LINC01140 in BC. LINC01140 expression in 1,085 breast cancer patients and 291 healthy subjects was analyzed from the Gene Expression Profiling Interactive Analysis website. The association between LINC01140 expression and T stages, LINC01140-related biological pathways, and the correlation between LINC01140 expression genes were also analyzed in 825 patients with BC through the cBioPortal database. The present study demonstrated that LINC01140 expression was significantly decreased in the tumor samples compared with normal samples in patients with BC (P<0.05). The present study revealed that LINC01140 expression was significantly decreased in the T4 stage compared with T1, T2 or T3 stage (P<0.01). In addition, high expression levels of LINC01140 predicts longer relapse-free survival probability in patients with BC. It was also observed that LINC01140 participates in a variety of biological pathways, particularly in the epithelial-to-mesenchymal transition. The co-expression relationship between the LINC01140 and an abundance of genes in samples from the BC study was investigated. These genes, such as chordin like 1 and bone morphogenic protein 6, participate in the development and progression of tumor growth and bone metastasis. Finally, the present study observed the interaction between microRNA (miR)-200b and miR-200c with LINC011440. The results from the present study indicated that higher expression of LINC01140 was beneficial for patients with BC. LINC01140 may be a potential biomarker for the prognosis of patients with BC. The role of LINC01140 in BC needs to be further evaluated.

The long noncoding RNA LINC01140/miR-140-5p/FGF9 axis modulates bladder cancer cell aggressiveness and macrophage M2 polarization.

MIBC (muscle invasive bladder cancer) only accounts for only a minority of bladder cancers, however, the disease-specific and overall survival rates of patients with MIBC are low. Macrophage M2 polarization has been reported to be associated with poorer prognosis in bladder cancer. Through cancer bioinformatics and experimental analyses, FGF9 was found to be upregulated in MIBC tissues. FGF9 knockdown in T24 cells strongly suppressed the viability, migratory capacity, and invasive capacity of cells; culture with medium from FGF9 knockdown T24 cells (si-FGF9-CM) significantly inhibited macrophage M2 polarization, while promoting M1 polarization. The long noncoding RNA (lncRNA) LINC01140 was positively correlated with FGF9 and was significantly upregulated in MIBC tissues. LINC01140 knockdown inhibited the viability, migratory capacity and invasive capacity of T24 cells; culture in si-LINC01140-CM also inhibited macrophage M2 polarization, while promoting M1 polarization. LINC01140 targeted miR-140-5p, while miR-140-5p targeted FGF9 to form a lncRNA-miRNA-mRNA axis. The effects of miR-140-5p inhibition on bladder cancer aggressiveness and macrophage M2 polarization were opposite to those of LINC01140 or FGF9 knockdown; additionally, miR-140-5p inhibition partially reversed the effects of LINC01140 knockdown on FGF9 protein levels, bladder cancer phenotype, and macrophage M2 polarization. In conclusion, LINC01140, miR-140-5p, and FGF9 form a lncRNA-miRNA-mRNA axis that modulates the bladder cancer phenotype, affects macrophage M2 polarization through the tumor microenvironment, and in turn affects bladder cancer cell aggressiveness.

LINC01140 regulates the proliferation and invasion of esophageal squamous cell carcinoma Eca109 cells via miR-452-5p/Wnt/β-catenin axis / 中国肿瘤生物治疗杂志

@# [摘 要] 目的： 探讨长链非编码RNA（lncRNA）LINC01140在食管鳞状细胞癌（esophageal squamous cell carcinoma，ESCC）组织及细胞中的表达及其对Eca109细胞增殖与侵袭的影响及其分子机制。方法：选取2012年3月至2015年5月河北医科大学第四医院收治的133例ESCC患者的临床资料和GEPIA数据库中收集的182例ESCC组织及286例食管正常黏膜组织的LINC01140表达数据，以及ESCC细胞系Kyse150、Eca109和TE13。用qPCR法检测癌组织和细胞中LINC01140的表达水平，分析其表达水平与患者临床病理特征及预后的关系。分别将pcDNA3.1-LINC01140、阴性对照（pcDNA3.1-NC）或miR-452-5p mimic及阴性对照（miR-NC）转染到Eca109细胞，MTS、Transwell实验分别检测细胞的增殖与侵袭能力。用双荧光报告基因实验及TOP/FOP报告基因系统检测LINC01140与miR-452-5p的靶向结合作用及LINC01140对Wnt/β-catenin通路活化水平的影响。结果：LINC01140在ESCC组织和细胞中表达均显著下调（均P<0.01），LINC01140低表达与ESCC患者年龄、淋巴结转移、TNM分期及OS密切相关（均P<0.05）。LINC01140过表达明显抑制Eca109细胞的增殖及侵袭能力（均P<0.01）。机制研究表明，LINC01140可能通过竞争结合miR-452-5p影响Wnt/β-catenin信号通路的活化水平继而调控Eca109细胞的恶性生物学行为。结论：LINC01140通过靶向miR-452-5p/Wnt/β-catenin轴促进ESCC细胞的增殖与侵袭能力，其有望成为ESCC患者靶向治疗的潜在靶点及预后评估的标志物。