Long noncoding RNA FEZF1-AS1 predicts poor prognosis and modulates pancreatic cancer cell proliferation and invasion through miR-142/HIF-1α and miR-133a/EGFR upon hypoxia/normoxia

Nowadays, pancreatic cancer (PC) remains the most lethal tumor, partially due to the invasive and treatment-resistant phenotype induced by the extent of hypoxic stress within the tumor tissue. According to previous studies, miR-142/HIF-1α and miR-133a/EGFR could modulate PC cell proliferation under hypoxic and normoxic conditions, respectively. In the present study, FEZF1-AS1, a recently described oncogenic long noncoding RNA, was predicted to target both miR-142 and miR-133a; thus, we hypothesized that FEZF1-AS1 might affect PC cell proliferation through these two axes under hypoxic or normoxic conditions. In PC cell lines, FEZF1-AS1 acted as an oncogene via promoting PC cell proliferation and invasion through miR-142/HIF-1α axis under hypoxic condition; however, FEZF1-AS1 failed to affect the protein levels of HIF-1α and VEGF under the normoxic condition, suggesting the existence of another signaling pathway under normoxic condition. As predicted by an online tool, FEZF1-AS1 could target miR-133a to inhibit its expression; under the normoxic condition, FEZF1-AS1 exerted its effect on PC cell lines through miR-133a/EGFR axis. Taken together, FEZF1-AS1 might be a promising target in controlling the aberrant proliferation and invasion of PC cell lines.     

Long noncoding RNA SOX21-AS1 regulates the progression of triple-negative breast cancer through regulation of miR-520a-5p/ORMDL3 axis

Recently, long noncoding RNAs (lncRNAs) have been reported as a new kind of controllers about cancer processes in biology. In spite of the dysregulation of lncRNAs in various kinds of cancers, only a little of the information was effective on the expression configuration and inner effects of lncRNAs in triple-negative breast cancer (TNBC). This study valued the expression of lncRNA SOX21-AS1 and the biological role it played in TNBC. In our research, SOX21-AS1 had a high expression in TNBC cell lines. The functional experiments showed that knockdown of SOX21-AS1 obviously restrained cell proliferation, migration, invasion, and epithelial-mesenchymal transition process and promoted cell apoptosis. Mechanistically, SOX21-AS1 was found to bind with miR-520a-5p. Besides, ORMDL3 was identified as a downstream target of miR-520a-5p, and the suppressed ORMDL3 expression induced by silenced SOX21-AS1 could be restored by miR-520a-5p inhibition. Further, data from rescue assays revealed that SOX21-AS1 could regulate the malignancy of TNBC via miR-520a-5p/ORMDL3 axis. All in all, we identified that SOX21-AS1 regulated the cellular process of TNBC cells via antagonizing miR-520a-5p availability to upregulate ORMDL3 expression.     

长非编码 RNA ILF3-AS1 通过调控 miR-130a-3p/PTEN轴抑制宫颈癌细胞的增殖

ILF3反义 RNA 1(ILF3 antisense RNA 1,ILF3-AS1)是一条定位于染色体 19p13.2的lncRNA,它是白介素增强子结合因子3(interleukin enhancer binding factor 3,ILF3)的反义 RNA.ILF3-AS1在多种肿瘤发生发展中发挥关键作用,但其...     

Long Non-coding RNA FEZF1-AS1 Promotes Growth and Reduces Apoptosis Through Regulation of miR-363-3p/PAX6 Axis in Retinoblastoma

Retinoblastoma is the most common malignancy in children's eyes with high incidence. Long non-coding RNAs (lncRNAs) play important roles in the progression of retinoblastoma. LncRNA FEZF1 antisense RNA 1 (FEZF1-AS1) has been found to stimulate retinoblastoma. However, the mechanism of FEZF1-AS1 underlying progression of retinoblastoma is still unclear. In current study, FEZF1-AS1 was up-regulated in retinoblastoma tissues and cells. FEZF1-AS1 overexpression enhanced retinoblastoma cell viability, promoted cell cycle, and inhibited apoptosis. Conversely, FEZF1-AS1 knockdown reduced cell viability, cycle, and elevated apoptosis. The interaction between FEZF1-AS1 and microRNA-363-3p (miR-363-3p) was confirmed. FEZF1-AS1 down-regulated miR-363-3p and up-regulated PAX6. PAX6 was a target gene of miR-363-3p. EZF1-AS1 promoted retinoblastoma cell viability and suppressed apoptosis via PAX6. Further, we demonstrated that FEZF1-AS1 contribute to tumor formation in vivo. In conclusion, FEZF1-AS1 elevated growth and inhibited apoptosis by regulating miR-363-3p/PAX6 in retinoblastoma, which provide a new target for retinoblastoma treatment.

     

LncRNA HAND2-AS1 exerts anti-oncogenic effects on ovarian cancer via restoration of BCL2L11 as a sponge of microRNA-340-5p

In the early stage of ovarian cancer (OC), molecular biomarkers are critical for its diagnosis and treatment. Nevertheless, there is little research on the mechanism underlying tumorigenesis in OC. Herein, we aimed to explore whether long noncoding RNA (lncRNA) HAND2-AS1 participated in the regulation of the cell proliferation, migration, and apoptosis of OC by regulating B-cell lymphoma 2 like 11 (BCL2L11) and microRNA-340-5p (miR-340-5p). Differentially expressed lncRNAs in OC were screened by microarray-based analysis. HAND2-AS1, BCL2L11, and miR-340-5p expression was assessed in normal ovarian and OC tissues and human OC cell lines. Then, the relationships among HAND2-AS1, BCL2L11, and miR-340-5p were explored. Ectopic expression and depletion experiments were applied to analyze the effects of HAND2-AS1, miR-340-5p and BCL2L11 on migration, invasion, and proliferation of OC cells, as well as apoptosis. Lastly, the tumor xenograft in nude mice was conducted to test the tumorigenesis in vivo. In silico analysis displayed poor expression of HAND2-AS1 in OC. HAND2-AS1 specifically sponged with miR-340-5p which was found to directly target BCL2L11. Importantly, HAND2-AS1 or BCL2L11 overexpression or miR-340-5p downregulation resulted in reduction of cell invasion and migration, together with decrease of cell proliferation and increase of cell apoptosis in OC. Besides, high-expressed HAND2-AS1 inhibited the tumorigenesis in nude mice. To sum up, these data suggests HAND2-AS1 as an anti-oncogene in OC through upregulation of BCL2L11 by competitively binding to miR-340-5p, which demonstrates that there are potential diagnosis and therapy values of HAND2-AS1 in OC.     

Long noncoding RNA FOXD3-AS1 promotes colon adenocarcinoma progression and functions as a competing endogenous RNA to regulate SIRT1 by sponging miR-135a-5p

More and more documents have proved that the abnormal expression of long noncoding RNAs (lncRNAs) are correlated with the initiation and progression of colorectal cancer (CRC). lncRNA FOXD3-AS1 has been reported in glioma for its oncogenic property. According to the survival analysis of The Cancer Genome Atlas database, FOXD3-AS1 upregulation implied lower survival rate of patients with CRC. Quantitative real-time polymerase chain reaction showed the overexpression of FOXD3-AS1 in both CRC tissues and cells. The Kaplan–Meier method demonstrated the prognostic value of FOXD3-AS1 for patients with CRC. To explore the effect of FOXD3-AS1 on CRC progression, loss-of-function experiments were carried out, whose results indicated that knockdown of FOXD3-AS1 suppressed cell proliferation, migration, and invasion, inhibited cell cycle and promoted cell apoptosis in vitro. In vivo experiments affirmed that FOXD3-AS1 affected tumor growth. FOXD3-AS1 expression was enriched in the cytoplasm of CRC cells. Mechanism experiments revealed that FOXD3-AS1 served as a competing endogenous RNA to upregulate SIRT1 by sponging miR-135a-5p. In addition, SIRT1 silencing also restrained cell proliferation and motility. Rescue assays revealed the biological function of FOXD3-AS1/miR-135a-5p/SIRT1 axis in CRC progression. In conclusion, FOXD3-AS1 promotes CRC progression by regulating miR-135a-5p/SIRT1 axis, shedding lights on the way to CRC treatments.     

Long noncoding RNA SOX21-AS1 promotes cervical cancer progression by competitively sponging miR-7/VDAC1

Growing evidence has shown that long noncoding RNAs (lncRNAs) play crucial roles in cervical cancer. Dy000sregulation of lncRNA SOX21 antisense RNA 1 (SOX21-AS1) has been reported in several tumors. However, its expression pattern and potential biological function in cervical cancer (CC) have not been investigated. In this study, we first reported that SOX21-AS1 expression was significantly upregulated in both CC tissues and cell lines. High expression of SOX21-AS1 was found to be significantly correlated with Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis and depth of cervical invasion. Further clinical assay confirmed that high SOX21-AS1 expression was associated with shorter overall survival and could be used as a potential prognostic biomarker for CC patients. Functional investigation showed that knockdown of SOX21-AS1 suppressed CC cells proliferation, migration, and invasion, as well as epithelial to mesenchymal transition progress. Furthermore, our data showed that microRNA-7 (miR-7) interacted with SOX21-AS1 by directly targeting the miRNA-binding site in the SOX21-AS1 sequence, and quantitative real-time polymerase chain reaction results showed overexpression of SOX21-AS1 decreased the levels of miR-7 in CC cells. Moreover, we confirmed that miR-7 directly targeted the 3′-untranslated region of voltage dependent anion channel 1 (VDAC1). Final in vitro assay suggested that in CC cells with SOX21-AS1, VDAC1 overexpression resulted in an increase of cell proliferation, migration, and invasion. Overall, our findings illuminate how SOX21-AS1 formed a regulatory network to confer an oncogenic function in CC and SOX21-AS1 could be regarded as an efficient therapeutic target and potential biomarker for CC patients.     

The lncRNA SNHG15/miR-18a-5p axis promotes cell proliferation in ovarian cancer through activating Akt/mTOR signaling pathway

Here, we report the expression pattern, function and regulatory mechanism of SNHG15 together with miR-18a-5p micro RNA in ovarian cancer (OC) for the first time. We recruited 20 patients and took normal ovarian tissues and ovarian tumor tissues from them. We used cell culture, transfection, in vivo tumor xenograft assay, and multiple types of detection assays to investigate the expression and regulation of long noncoding RNA (lncRNA) SNHG15/miR-18a-5p in ovarian tissues and cells. Results: We found that the messenger RNA expression level of SNHG15 was significantly higher and miR-18 was decreased in ovarian cancer tissues and in OC cells. Functional experiments showed that SNHG15 overexpression potentiated the migration and invasion of OC cells, while SNHG15 inhibition reduced the tumor proliferation, which was restored via overexpression of miR-18a. SNHG15 was found to directly target and suppress the expression of miR-18a. Our results illustrate the possible molecular mechanism of lncRNA SNHG15/miR-18a-5p functions in cell proliferation in OC. SNHG15/miR-18a promoted the progression of OC cells via the protein kinase B/mammalian target of rapamycin signaling pathway.     

MiR-526b targets lncRNA SLC16A1-AS1 to suppress cell proliferation in triple-negative breast cancer

The present study investigated the potential interaction between miR-526b and lncRNA SLC16A1-AS1 in triple-negative breast cancer (TNBC). Expression of miR-526b and SLC16A1-AS1 in TNBC tumor tissues and paired nontumor tissues from 60 TNBC patients was detected by real-time polymerase chain reaction (RT-qPCR). The interaction between miR-526b and SLC16A1-AS1 was evaluated with overexpression experiments, followed by RT-qPCR. The proliferation and migration of cells were detected with cell counting kit-8 assay and Transwell assay, respectively. Apoptosis of cells was assessed by cell apoptosis assay. The expression of apoptosis-related proteins was quantified by Western blot analysis. MiR-526b was predicted to bind with SLC16A1-AS1. Overexpression of miR-526b in TNBC cells decreased the expression levels of SLC16A1-AS1, while overexpression of SLC16A1-AS1 did not affect the expression of miR-526b. In TNBC tissues, miR-526b was downregulated in TNBC tissues, while SLC16A1-AS1 was upregulated in TNBC tissues compared to that in nontumor tissues. The expression of SLC16A1-AS1 and miR-526b were inversely correlated. In vitro experiments showed that overexpression of SLC16A1-AS1 promoted cell proliferation and invasion but suppressed cell apoptosis. MiR-526b played an opposite role and suppressed the function of SLC16A1-AS1. MiR-526b is downregulated in TNBC and it targets SLC16A1-AS1 to regulate proliferation, apoptosis, and invasion of TNBC cells.     

The lncRNA ZEB1-AS1 sponges miR-181a-5p to promote colorectal cancer cell proliferation by regulating Wnt/β-catenin signaling

Long noncoding RNAs (lncRNAs) are important regulators of the biological functions and underlying molecular mechanisms of colorectal cancer (CRC). However, the role of the lncRNA ZEB1-AS1 in CRC is not thoroughly understood. In this study, we found that ZEB1-AS1 was markedly upregulated in CRC. ZEB1-AS1 knockdown significantly suppressed CRC cell proliferation and induced apoptosis, whereas enhanced expression of ZEB1-AS1 had the opposite effect. Bioinformatics analysis identified miR-181a-5p as a candidate target of ZEB1-AS1. Moreover, we found an inverse correlation between ZEB1-AS1 and miR-181a-5p expression in CRC tissue. Inhibition of miR-181a-5p significantly upregulated ZEB1-AS1, whereas overexpression of miR-181a-5p had the opposite effect, suggesting that ZEB1-AS1 is negatively regulated by miR-181a-5p. Using luciferase reporter and RIP assays, we found that miR-181a-5p directly targets ZEB1-AS1. Importantly, ZEB1-AS1 may act as an endogenous ‘sponge’ to regulate miRNA targets by competing for miR-181a-5p binding. In summary, our findings provide the evidence supporting the role of ZEB1-AS1 as an oncogene in CRC. Our study also demonstrates that miR-181a-5p targets not only protein-coding genes but also the lncRNA ZEB1-AS1.     

Long noncoding RNA SBF2-AS1 promotes colorectal cancer proliferation and invasion by inhibiting miR-619-5p activity and facilitating HDAC3 expression

Evidence, demonstrating long noncoding RNAs (lncRNAs) as critical players in cancer, remains to increase. lncRNA SBF2-AS1 was reported to be involved in several cancers, such as hepatocellular carcinoma. However, the role of SBF2-AS1 in colorectal cancer (CRC) is unknown. We showed lncRNA SBF2-AS1 expression was growing in CRC samples, especially in advanced cases. Accordingly, SBF2-AS1 possesses higher expression in CRC cell lines than in normal cell line. Moreover, SBF2-AS1 high expression indicated a low survival rate. Functionally, SBF2-AS1 knockdown suppressed the proliferation, migration, and invasion of CRC cells. In terms of mechanism, SBF2-AS1 upregulation restrained the activity of miR-619-5p and led to overexpression of HDAC3. Importantly, downregulation of miR-619-5p or HDAC3 overexpression reversed SBF2-AS1-silencing-caused suppression on proliferation and metastasis. Summarily, our findings elucidated a crucial role of SBF2-AS1 as a miR-619-5p sponge, shedding novel light on lncRNA-related prognostics.     

MiR-1204 promotes ovarian squamous cell carcinoma growth by increasing glucose uptake

MiR-1204 has been recently identified as an oncogenic miRNA in breast cancer. Our study aims to investigate the role of miR-1204 in ovarian squamous cell carcinoma. Expression of miR-1204 and glucose transporter 1 in ovarian biopsies and plasma of both OC patients and healthy controls was detected by qRT-PCR. Correlations between patients’ clinicopathological data were analyzed by Chi-square test. MiR-1204 overexpression OC cell lines were established. Expression of GLUT-1 protein was detected by western blot. Glucose uptake was measured by glucose uptake assay. Cell proliferation was detected by CCK-8 assay. We found that miR-1204 expression was significantly correlated with tumor size. Expression levels of miR-1204 and GLUT-1 were significantly high in OC patients. Expression levels of miR-1204 were positively correlated with expression levels of GLUT-1 in OC patients. MiR-1204 overexpression significantly promoted GLUT-1 expression, glucose uptake and cell proliferation. MiR-1204 may promote ovarian squamous cell carcinoma growth by increasing glucose uptake.     

Overexpression miR-520a-3p inhibits acute myeloid leukemia progression via targeting MUC1

BackgroundAcute myeloid leukemia (AML) is one of the familiar malignant tumors in the hematological system. miR-520a-3p is reported to be involved in several cancers’ progression. However, miR-520a-3p role in AML remains unclear. In this study, we aimed to clarify the role and potential mechanism of miR-520a-3p in AML.MethodsCell viability, proliferation, cycle and apoptosis were detected by MTT assay, colony formation assay, flow cytometry, respectively. The levels of PNCA, Bcl-2, Cleaved caspase 3, Cleaved caspase 9 and β-catenin protein were detected by Western blot. Dual-luciferase reported assay was performed to detect the regulation between miR-520a-3p and MUC1. To verify the effect of miR-520a-3p on tumor proliferation in vivo, a non-homogenous transplant model of tumors was established.ResultsmiR-520a-3p expression was down-regulated, and MUC1 expression was up-regulated in AML patients. miR-520a-3p overexpression suppressed THP-1 cell proliferation, induced cell cycle G0/G1 inhibition and promoted apoptosis. miR-520a-3p targeted MUC1 and negatively regulated its expression. MUC1 knockdown inhibited THP-1 cell proliferation and promoted apoptosis. miR-520a-3p overexpression inhibited AML tumors growth.ConclusionOverexpression miR-520a-3p inhibited AML cell proliferation, and promoted apoptosis via inhibiting MUC1 expression and repressing Wnt/β-catenin pathway activation.     

Long noncoding RNA DLX6-AS1 promotes liver cancer by increasing the expression of WEE1 via targeting miR-424-5p

Long noncoding RNAs (lncRNAs) played an important role in tumorigenesis and development of hepatocellular carcinoma (HCC). In this study, we first demonstrated that lncRNA DLX6 antisense RNA 1 (DLX6-AS1) was upregulated in cancer tissues and cells lines compared with normal adjacent and cell line. Knock-down DLX6-AS1 by transfection with small interfering RNA (siRNA) suppressed cell proliferation, migration, and invasion of HCC cells. Cell cycle analysis showed that cells transfected with siRNA were arrested in G0/G1 phase. Then, we performed dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay to show that DLX6-AS1 could bind with miR-424-5p. And cotransfection inhibitor of miR-424-5p with siRNA of DLX6-AS1 could abolish the inhibitory effect of siRNA of DLX6-AS1 on cell proliferation, migration, and invasion. Moreover, we further demonstrated that the oncogene WEE1 G2 checkpoint kinase (WEE1) was the target of miR-424-5p and expression levels of WEE1 were positive correlation with that of DLX6-AS1. Taken together, these results suggested that upregulated DLX6-AS1 promoted cell proliferation, migration, and invasion of HCC through increasing expression of WEE1 via targeting miR-424-5p.     

p53/miR-30a-5p/ SOX4 feedback loop mediates cellular proliferation,apoptosis, and migration of non-small-cell lung cancer

Many microRNAs (miRNAs) play vital roles in the tumorigenesis and development of cancers. In this study, we aimed to identify the differentially expressed miRNAs and their specific mechanisms in non-small-cell lung cancer (NSCLC). Based on data from the GSE56036 database, miR-30a-5p expression was identified to be downregulated in NSCLC. Further investigations showed that overexpression of miR-30a-5p inhibited cell proliferation, migration, and promoted apoptosis in NSCLC. Increase of miR-30a-5p level could induce the increase of Bax protein level and decrease of Bcl-2 protein level. In addition, chromatin immunoprecipitation assays showed that miR-30a-5p expression was induced by binding of p53 to the promoter of MIR30A. Bioinformatics prediction indicated that miR-30a-5p targets SOX4, and western blot analysis indicated that overexpression of the miRNA decreases the SOX4 protein expression level, which in turn regulated the level of p53. Thus, this study provides evidence for the existence of a p53/miR-30a-5p/SOX4 feedback loop, which likely plays a key role in the regulation of proliferation, apoptosis, and migration in NSCLC, highlighting a new therapeutic target.     

细胞周期蛋白依赖性激酶在miR-193a5p调控卵巢癌细胞增殖及上皮细胞间充质转变中的作用*

目的: 探讨miR-193a-5p靶向CDK14并调控卵巢癌细胞OVAC的增殖和上皮间充质转变(EMT)的作用。方法: 通过TargetScanHuman分析miR-193a-5p与CDK14的匹配情况,通过荧光素酶报告系统检测miR-193a-5p靶向CDK14情况;在miR-193a-5p mimics过表达或者miR-193a-5p inhibitor基因沉默miR-193a-5p的情况下,采用免疫印迹检测CDK14,EMT相关蛋白质E-cadherin、vimentin、fibronectin和N-cadherin的表达量,采用CCK-8检测卵巢癌细胞OVAC增殖情况, MMT检测卵巢癌细胞OVAC的细胞活力。结果: miR-193a-5p靶向CDK14的3‘UTR;过表达miR-193a-5后, CDK14的表达下降,EMT相关蛋白质E-cadherin的表达上升,vimentin、fibronectin和N-cadherin的表达下降,卵巢癌细胞OVAC的增殖和细胞活力均增加;同时,基因沉默miR-193a-5p后, CDK14的表达上升,EMT相关蛋白质E-cadherin的表达下降,vimentin、fibronectin和N-cadherin的表达量上升,卵巢癌细胞OVAC的增殖和细胞活力均减少。结论: miR-193a-5p通过靶向CDK14的3‘UTR降低卵巢癌细胞OVAC的增殖、细胞活力和EMT。     

HOXC13-AS promotes breast cancer cell growth through regulating miR-497-5p/PTEN axis

Dysregulated long noncoding RNAs (lncRNAs) remains to be explored in tumorigenesis. LncRNA HOXC13 antisense RNA (HOXC13-AS) has been found as an oncogene in many cancers; however, the role of HOXC13-AS in breast cancer still elusive. In this study, the HOXC13-AS levels and its role in cell proliferation was first measured by real-time quantitative polymerase chain reaction, Cell Counting Kit-8 assay, and colony formation assay. It showed that HOXC13-AS was increased in breast cancer tissues compared with the adjacent normal tissues and upregulated HOXC13-AS promoted the growth of breast cancer cells. Then, we found that the miR-497-5p levels were downregulated in cancer tissues compared with the adjacent tissues and miR-497-5p suppressed breast cancer cell proliferation. Further study showed that HOXC13-AS could function as a “sponge” for miR-497-5p then suppress miR-497-5p expression. Moreover, we next identified that Phosphatase and Tensin homolog (PTEN) is the target of miR-497-5p. Overexpression of miR-497-5p by chemical mimics decreased the expression of PTEN, while downregulation of miR-497-5p by HOXC13-AS rescued the expression of PTEN. Finally, we showed that HOXC13-AS promoted the proliferation of breast cancer cells and tumor growth through miR-497-5p/PTEN axis in vitro and in vivo. Hence, we conclude that HOXC13-AS, which is significantly upregulated in breast cancers, promoted cell proliferation through the suppressed miR-497-5p and further upregulated PTEN.