Integrative analysis of OIP5-AS1/HUR1 to discover new potential biomarkers and therapeutic targets in multiple sclerosis

Multiple sclerosis (MS) is a devastating autoimmune disease of the central nervous system associated with demyelination and axonal injury. This study was designed to find potential lncRNAs and their targets that are associated with the molecular basis of MS pathogenesis. In this study, peripheral blood samples were obtained from 50 relapsing-remitting MS (RR-MS) patients and 50 healthy controls. lncRNAs and their target were selected for validation using TaqMan Real-Time PCR. Interactions were studied based on approaches that used to investigation biological functions and signaling pathways affected by differentially expressed messenger RNAs (mRNAs). The results of this study indicate an increase in the expression of HUR1 (p = 0.0001), CPSF7 (p = 0.02), and reduction of CSTF2 expression (p = 0.04). Also, an increase in the expression of OIP5-AS1 (p = 0.01) was observed in men less than 30 years old. We performed a comparative analysis of the long noncoding RNAs (lncRNAs), and then we ranked them as candidate biomarkers according to a decreasing area under the receiver operating characteristic (ROC) curve (AUC) and plotted the results. Dysregulation of lncRNA expression has been linked to diseases. Further studies on the HUR1 gene can be used as diagnostic tools for the identification of high-risk individuals in families with a history of disease before, during, and even after treatment. Our data uncovered the expression profiles of lncRNAs and mRNAs in MS patients, which will help delineate the molecular mechanisms in MS pathogenesis. However, further studies need to determine the precise role of these genes in the pathological process in MS.     

Abnormally expressed long noncoding RNA B3GALT5-AS1 may serve as a biomarker for the diagnostic and prognostic of gastric cancer

Early diagnosis of gastric cancer (GC) is an effective method to improve prognosis. Increasing number of long noncoding RNAs (lncRNAs) have been reported as biomarkers for several cancers. We aim to detect the level of lncRNA B3GALT5-AS1 and its association with clinical parameters and to further explore its application value in GC. We measured serum B3GALT5-AS1 expression in 107 patients with GC, 40 polyp patients, and 87 normal controls to explore the significance of serum B3GALT5-AS1 in GC using the quantitative real-time polymerase chain reaction method. The result demonstrated that B3GALT5-AS1 level was markedly richer in GC patients than that in normal people (P < .001). B3GALT5-AS1 may be served as a diagnostic marker for distinguishing GC patients from healthy people, and the proportion under the receiver operating characteristics curve is 0.816 (95% confidence interval, 0.758-0.874; P = .03). Further exploration validated that high serum B3GALT5-AS1 level was related to TNM stage (P = .024), and lymph node metastasis (P = .023). Our study suggested that serum B3GALT5-AS1 may be employed as an ideal biomarker for early screening of GC.     

IncRNA MAPKAPK5-AS1 promotes proliferation and migration of thyroid cancer cell lines by targeting miR-519e-5p/YWHAH

Thyroid cancer is a common malignant tumour of the endocrine system and ranks ninth in cancer incidence worldwide. An extensive body of evidence has demonstrated that lncRNAs play a critical role in the progression of thyroid cancer. The lncRNA MAPKAPK5-AS1 has been reported to be abnormally expressed and to play a role in the development of various human cancers. However, MAPKAPK5-AS1’s potential role in thyroid cancer progression remains unknown. The objective of our study was to explore the role and mechanism of MAPKAPK5-AS1 in thyroid cancer cells and provide a potential target for its biological diagnosis and treatment. We transfected sh-MAPKAPK5-AS1 and sh-NC into BCPAP and TPC-1 cells for loss-of-function assays. Results of RT-qPCR analysis demonstrated that MAPKAPK5-AS1 was more highly expressed in thyroid cancer cells compared to normal cells. Functional assays demonstrated that interfering with the expression of MAPKAPK5-AS1 notably repressed proliferation and invasion and accelerated apoptosis of BCPAP and TPC-1 cells. Mechanistically, we found that miR-519e-5p was negatively regulated by MAPKAPK5-AS1 and that tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH) was a target of miR-519e-5p. Additionally, rescue assays demonstrated that downregulation of MAPKAPK5-AS1 expression inhibited cell proliferation, migration, and invasion and promoted apoptosis by sponging miR-519e-5p, thereby increasing YWHAH expression. Ultimately, our study revealed that MAPKAPK5-AS1 promotes proliferation and migration of thyroid cancer cells by targeting the miR-519e-5p/YWHAH axis, which provides novel insight into the development and progression of thyroid cancer.Key words: IncRNA MAPKAPK5-AS1, MiR-519e-5p, YWHAH, thyroid cancer cell     

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.     

SBF2-AS1: An oncogenic lncRNA in small-cell lung cancer

The long noncoding RNAs (lncRNAs) SBF2 antisense RNA 1 (SBF2-AS1) was found to act as an oncogenic lncRNA in non–small-cell lung cancer (NSCLC), but the role of SBF2-AS1 in small-cell lung cancer (SCLC) was still unclear. The purpose of this study was to provide the clinical significance and biological function of SBF2-AS1 in SCLC. In our results, SBF2-AS1 was found to be upregulated in SCLC tissues compared with NSCLC tissues or adjacent normal lung tissues. Besides, SBF2-AS1 expression was also elevated in SCLC cell lines compared with the normal bronchial epithelial cell line or NSCLC lines. Moreover, high expression of SBF2-AS1 was associated with clinical stage, tumor size, lymph node metastasis and distant metastasis in SCLC patients. Survival analysis showed SCLC patients with high expression of SBF2-AS1 had shorter overall survival than patients with low expression of SBF2-AS1, and high expression of SBF2-AS1 acted as an independent poor prognostic factor for overall survival in SCLC patients. The study in vitro suggested inhibition of SBF2-AS1 obviously depressed cell proliferation, migration, and invasion in SCLC. In conclusion, SBF2-AS1 acts as a novel oncogenic lncRNA in SCLC.     

LncRNA F11-AS1 suppresses liver hepatocellular carcinoma progression by competitively binding with miR-3146 to regulate PTEN expression

Accumulating evidence has proved that long noncoding RNAs (lncRNAs) are involved in cancer progression. The abnormal expression of lncRNAs might mediate cancer in various ways. Liver hepatocellular carcinoma (LIHC) is the third leading cause of tumor-related deaths. Due to the difficulty in its early recognition, the therapeutic outcomes of LIHC are far from satisfactory. The lncRNA Coagulation Factor XI Antisense RNA 1 (F11-AS1) is underexpressed in LIHC and suppresses LIHC progression in return. F11-AS1 can bind with and negatively regulate miR-3146, while miR-3146 can bind with and negatively regulate PTEN. Moreover, F11-AS1 positively regulates the messenger RNA and protein level of PTEN. Also, miR-3146, F11-AS1, and PTEN could all be immunoprecipitated by antibody against Ago2, indicating the existence of RNA–induced silencing complex. Therefore, F11-AS1 mediates PTEN expression by acting as competing endogenous RNA of miR-3146. Further rescue assays demonstrated that F11-AS1 suppressed LIHC progression via such pattern. To sum up, F11-AS1 suppresses LIHC progression by competitively binding with miR-3146 to regulate PTEN expression. The F11-AS1/miR-3146/PTEN axis is brand new. Taken together, the results indicate that F11-AS1 might serve as a therapeutic target of LIHC.     

Long noncoding RNA DLGAP1-AS1 promotes cell proliferation in hepatocellular carcinoma via sequestering miR-486-5p

Hepatocellular carcinoma (HCC) is most prevalent tumor in liver and one of the most fatal cancers in the world. Long noncoding RNAs (lncRNAs) have been accepted as important regulators in carcinomas. But there are still many lncRNAs including DLGAP1-AS1 unannotated in HCC. First of all, GEPIA suggested that DLGAP1-AS1 presented high expression in HCC tissue samples relative to the normal tissues. Besides, overexpression of DLGAP1-AS1 was also proved in HCC cell lines. Moreover, DLGAP1-AS1 knockdown efficiently suppressed cell proliferation in HCC. Interestingly, miR-486-5p was predicted and validated to interact with DLGAP1-AS1, while the level of miR-486-5p was significantly increased In HCC after DLGAP1-AS1 knockdown. Moreover, we uncovered that ectopic expression of miR-486-5p induced suppression on HCC cell proliferation and that miR-486-5p inhibition offset the effect of DLGAP1-AS1 silence on HCC cell proliferation and apoptosis. Furthermore, H3F3B was identified as target of miR-486-5p and was therefore positively regulated by DLGAP1-AS1 in HCC. Of note, H3F3B upregulation partly revived the declined cell proliferative capacity in response to DLGAP1-AS1 knockdown. To conclude, DLGAP1-AS1 exerted its oncogenic role in HCC via miR-486-5p/H3F3B axis. Our new findings provided novel theoretical basis for discovery of therapeutic targets of HCC.     

LncRNA TP73-AS1 is a novel regulator in cervical cancer via miR-329-3p/ARF1 axis

Cervical cancer holds one of the highest morbidity and mortality in various types of cancers. It even leads to the most number of cancer-related deaths of women. A lot of research has indicated that the anomalous expression of long noncoding RNAs (lncRNAs) would induce carcinogenesis and is associated with poor prognosis of patients with cancer. However, the function and mechanism of many lncRNAs still call for further research. Tumor Protein P73 Antisense RNA 1 (TP73-AS1) is no exception. LncRNA TP73-AS1 has been found to promote cancer progressions in various cancers. It is upregulated in cervical cancer cells. The proliferation and migration ability of cervical cancer cells can also be boosted by TP73-AS1 in return. Meanwhile, miRNA-329-3p is downregulated in cervical cancer cells and could bind with both TP73-AS1 and ADP Ribosylation Factor 1 (ARF1). TP73-AS1 inhibited miR-329-3p expression while miR-329-3p inhibited ARF1 expression. More importantly, TP73-AS1 can positively regulate ARF1 expression. Based on all these experiments, TP73-AS1 regulates ARF1 expression by competitively binding with miR-329-3p, thus regulating cervical cancer progression. Further rescue assays confirmed TP73-AS1 regulates cervical cell proliferation and migration via miR-329-3p/ARF1. TP73-AS1 might serve as a novel regulator in cervical cancer.     

LncRNA MNX1-AS1 promotes the progression of cervical cancer through activating MAPK pathway

Long noncoding RNAs (lncRNAs) have been discovered as significant regulators in a wide range of human cancers. Among them, lncRNA MNX1-AS1 has been proved to be an oncogene in ovarian cancer and glioblastoma. However, the regulatory mechanism of MNX1-AS1 in cervical cancer remains to be understood. Therefore, this study planned to explore the role of MNX1-AS1 in cervical cancer. In the beginning, we found that the expression of MNX1-AS1 was obviously upregulated in cervical cancer tissues and cell lines. Kaplan-Meier survival analysis revealed that patients with higher MNX1-AS1 expression level suffered from shorter overall survival time than those with lower MNX1-AS1 level. Moreover, by loss-of-function and gain-of-function assay, the effect of MNX1-AS1 on cell proliferation and apoptosis was examined on cellular level. Results showed that the proliferation of Hela cells was significantly inhibited and apoptosis enhanced by the transfection of shMNX1-AS1, while overexpressing MNX1-AS1 in E6E7 cells presented the contrary results. As for mechanism investigation, it was demonstrated that overexpression of MNX1-AS1 significantly improved the expression of p-ERK1/2 and p-JNK. And the effects of MNX1-AS1 on cell proliferation and apoptosis would be diminished after inactivating the phosphorylation of either ERK or JNK. Taken together, it was identified that MNX1-AS1 promoted proliferation and inhibited apoptosis of cervical cancer cells through MAPK pathway.     

LncRNA OIP5-AS1 regulates radioresistance by targeting DYRK1A through miR-369-3p in colorectal cancer cells

Object

This study aimed to investigate the role of lncRNA OIP5-AS1 in regulating radioresistance of colorectal cancer (CRC) cells.

Microarray expression profiles analysis revealed lncRNA OXCT1-AS1 promoted bladder cancer cell aggressiveness via miR-455-5p/JAK1 signaling

Bladder cancer (BCa) is one of the most prevalent cancers of the urinary system worldwide. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) perform a vital function in the pathogenesis and progression of BCa. In the current study, we identified a novel lncRNA OXCT1-AS1 and investigated its role and potential mechanisms in BCa. The microarray results showed the expression of lncRNAs, microRNAs, and messenger RNAs between BCa primary tumor tissues and metastatic lymph nodes were significantly different. The quantitative polymerase chain reaction verification was performed to ensure the reliability of the screening results. The Cell Counting Kit 8 and transwell assay were used to assess the tumor cell proliferation and invasion abilities in vitro, respectively. The dual-luciferase activity assay was performed to investigate the potential mechanism of competing endogenous RNA network. lncRNA OXCT1-AS1, which elevated in metastasis lymph node, was significantly upregulated in BCa cell lines compared with SVHUC-1. We demonstrated OXCT1-AS1 inhibited miR-455-5p to decrease its binding to the JAK1 3′-untranslated region, which could upregulate the expression of JAK1 at the protein level, thus promoting BCa proliferation and invasion. Therefore, lncRNA OXCT1-AS1 could act as a potential biomarker and therapeutic target for patients with BCa.     

Long noncoding RNA FLVCR1-AS1 aggravates biological behaviors of glioma cells via targeting miR-4731-5p/E2F2 axis

Long noncoding RNAs (lncRNAs) display essential roles in cancer progression. FLVCR1-AS1 is a rarely investigated lncRNAs involved in various human cancers, such as hepatocellular carcinoma and lung cancer. However, its function in glioma has not been clarified. In our study, we found that FLVCR1-AS1 was highly expressed in glioma tissues and cell lines. And upregulation of FLVCR1-AS1 predicted poor prognosis in patients with glioma. Moreover, FLVCR1-AS1 knockdown inhibited proliferation, migration and invasion of glioma cells. Through bioinformatics analysis, we identified that FLVCR1-AS1 was a sponge for miR-4731-5p to upregulate E2F2 expression. Moreover, rescue assays indicated that FLVCR1-AS1 modulated E2F2 expression to participate in glioma progression. Altogether, our research demonstrates that the FLVCR1-AS1/miR-4731-5p/E2F2 axis is a novel signaling in glioma and may be a potential target for tumor therapy.     

LncRNA ARAP1-AS1 aggravates the malignant phenotypes of ovarian cancer cells through sponging miR-4735-3p to enhance PLAGL2 expression

Ovarian cancer is one of the leading lethal gynecological cancers, causing serious harm to the health of female populations. Growing studies emphasize that lncRNAs serve as significant regulators in the tumorigenesis and evolution of numerous malignancies, including ovarian cancer. Recently, the oncogenic activity of lncRNA ARAP1-AS1 has been justified in a variety of cancers. However, the potential function of ARAP1-AS1 in ovarian cancer development is still unclear. Herein, we firstly revealed the expression profile of ARAP1-AS1 in ovarian cancer. Compared to normal samples and cells, upregulation of ARAP1-AS1 was observed in tissues and cells of ovarian cancer. Therewith, it was disclosed that knockdown of ARAP1-AS1 alleviated the carcinogenicity of ovarian cancer cells. Besides, our findings delineated that ARAP1-AS1 silence inhibited the expression of oncogene PLAGL2. Considering that ARAP1-AS1 was principally expressed in the the cytoplasm of ovarian cancer cells, we speculated that ARAP1-AS1 facilitated ovarian cancer progression via functioning as a ceRNA. Further investigations indicated that ARAP1-AS1 promoted PLAGL2 expression by competitively binding with miR-4735-3p. Of note, ARAP1-AS1 contributed to the malignant phenotypes of ovarian cancer cells through modulation of miR-4735-3p/PLAGL2 axis, revealing ARAP1-AS1 as a promising therapeutic target for ovarian cancer patients.

     

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.     

lncRNA ZFPM2-AS1 promotes proliferation via miR-18b-5p/VMA21 axis in lung adenocarcinoma

Lung cancer has been proved to be one of the most common kinds of cancers around the globe. Meanwhile, as the predominant type of lung cancer, lung adenocarcinoma (LUAD) has received increasing attention in cancer research. Long noncoding RNAs (lncRNAs) are known to be associated with oncogenesis and progression of various cancers. However, many lncRNAs have not been thoroughly detected in LUAD. In this study, through bioinformatics analysis we found that zinc finger protein multitype 2 antisense RNA 1 (ZFPM2-AS1) was associated with poor prognosis of LUAD patients. Also, ZFPM2-AS1 was detected to be overexpressed in LUAD tissues and cells. Furthermore, ZFPM2-AS1 could promote the proliferation of LUAD cells. Next, miR-18b-5p was found to bind with and negatively regulated by ZFPM2-AS1. VMA21, target gene of miR-18b-5p, could bind with and be negatively regulated by miR-18b-5p. More importantly, both ZFPM2-AS1 and VMA21 were found to be attached to the RNA-induced silencing complex constructed from miR-18b-5p and Ago2. Also, ZFPM2-AS1 could regulate the expression of VMA21. Therefore, ZFPM2-AS1 were confirmed to regulate VMA21 by competitively binding with miR-18b-5p. Finally, rescue assays confirmed that ZFPM2-AS1 could regulate LUAD cell proliferation via miR-18b-5p/VMA21 axis.