Long noncoding RNA FOXD2-AS1 promotes glioma cell cycle progression and proliferation through the FOXD2-AS1/miR-31/CDK1 pathway

Long noncoding RNAs (lncRNAs) are vital mediators involved in cancer progression. Previous studies confirmed that FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is upregulated in tumor diseases. The potential influence of FOXD2-AS1 in glioma progression, however, remains unknown. In this paper, FOXD2-AS1 was found to be upregulated in glioma tissues. Its level was linked with glioma stage. Moreover, glioma patients expressing high level of FOXD2-AS1 suffered worse prognosis. Biological functions of FOXD2-AS1 in glioma cells were analyzed through integrative bioinformatics and TCGA RNA sequencing data analysis. Pathway enrichment analysis uncovered that FOXD2-AS1 was mainly linked with cell cycle regulation in both low-grade glioma and glioblastoma. Further experiments demonstrated that silence of FOXD2-AS1 inhibited proliferation, arrested cell cycle and downregulated cyclin-dependent kinase 1 (CDK1) in human glioma cells. Dual-luciferase reporter assay confirmed that FOXD2-AS1 upregulated CDK1 by sponging miR-31. Rescue assays were performed and confirmed the regulatory loop FOXD2-AS1/miR-31/CDK1 in glioma. Collectively, our results indicated that the FOXD2-AS1/miR-31/CDK1 axis influenced glioma progression, providing a potential new target for glioma patients.     

lncRNA HOXB-AS3 exacerbates proliferation,migration, and invasion of lung cancer via activating the PI3K-AKT pathway

Lung cancer remains the leading cause of cancer-related death all over the world. In spite of the great advances made in surgery and chemotherapy, the prognosis of lung cancer patients is poor. A substantial fraction of long noncoding RNAs (lncRNAs) can regulate various cancers. A recent study has reported that lncRNA HOXB-AS3 plays a critical role in cancers. However, its biological function remains unclear in lung cancer progression. In the current research, we found HOXB-AS3 was obviously elevated in NSCLC tissues and cells. Functional assays showed that inhibition of HOXB-AS3 was able to repress A549 and H1975 cell proliferation, cell colony formation ability and meanwhile, triggered cell apoptosis. Furthermore, the lung cancer cell cycle was mostly blocked in the G1 phase whereas the cell ratio in the S phase was reduced. Also, A549 and H1975 cell migration and invasion capacity were significantly repressed by the loss of HOXB-AS3. The PI3K/AKT pathway has been implicated in the carcinogenesis of multiple cancers. Here, we displayed that inhibition of HOXB-AS3 suppressed lung cancer cell progression via inactivating the PI3K/AKT pathway. Subsequently, in vivo experiments were utilized in our study and it was demonstrated that HOXB-AS3 contributed to lung cancer tumor growth via modulating the PI3K/AKT pathway. Overall, we implied that HOXB-AS3 might provide a new perspective for lung cancer treatment via targeting PI3K/AKT.     

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.     

Long noncoding RNA FAM83H‐AS1 exerts an oncogenic role in glioma through epigenetically silencing CDKN1A (p21)

Gliomas are the commonest and most aggressive primary malignant tumor in the central nervous system. Long noncoding RNAs (lncRNAs) have been identified to act as crucial regulators in multiple biological processes, including tumorigenesis. FAM83H antisense RNA1 (FAM83H‐AS1) has been uncovered to be dysregulated in several cancers. However, the biological role of FAM83H‐AS1 in glioma still needs to be investigated. Currently, our findings indicated that FAM83H‐AS1 was upregulated in glioma tissues and cell lines and high level of FAM83H‐AS1 was associated with poor prognosis of glioma. Loss‐of‐function assays demonstrated that silenced FAM83H‐AS1 obviously suppressed cell proliferation via regulating the cell‐cycle distribution and cell apoptosis rate, and mechanistic experiments revealed that FAM83H‐AS1 could epidemically silence CDKN1A expression through recruiting EZH2 to the promoter of CDKN1A, thereby influencing the cell cycle and proliferation. Collectively, our findings suggested that FAM83H‐AS1 participated in the progression of glioma and might act as a potential therapeutic target and prognosis biomarker for human glioma.     

The long noncoding RNA ZFAS1 promotes the progression of glioma by regulating the miR-150-5p/PLP2 axis

Numerous studies have reported that long noncoding RNA (lncRNA) dysregulation is involved in the progression of many malignant tumors, including glioma. The lncRNA ZNFX1 antisense RNA 1 (ZFAS1) plays an oncogenic role in various malignant tumors, such as gastric cancer and hepatocellular carcinoma. However, the underlying molecular mechanism of ZFAS1 in glioma has not been fully clarified. In this study, we found that the expression of ZFAS1 was upregulated in both glioma tissues and cell lines. Functional experiments revealed that ZFAS1 promoted glioma proliferation, migration and invasion, and increased resistance to temozolomide in vitro. By using online databases, RNA pull-down assays and luciferase reporter assays, ZFAS1 was demonstrated to act as a sponge of miR-150-5p. Furthermore, proteolipid protein 2 (PLP2) was shown to be the functional target of miR-150-5p. Rescue experiments revealed that ZFAS1 regulated the expression of PLP2 by sponging miR-150-5p. Finally, a xenograft tumor assay demonstrated that ZFAS1 promoted glioma growth in vivo. Our results showed that ZFAS1 promoted glioma malignant progression by regulating the miR-150-5p/PLP2 axis, which may provide a potential therapeutic target for the treatment of glioma.     

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 LINC00998 inhibits the malignant glioma phenotype via the CBX3-mediated c-Met/Akt/mTOR axis

Long noncoding RNAs (lncRNAs), once considered to be nonfunctional relics of evolution, are emerging as essential genes in tumor progression. However, the function and underlying mechanisms of lncRNAs in glioma remain unclear. This study aimed to investigate the role of LINC00998 in glioma progression. Through screening using TCGA database, we found that LINC00998 was downregulated in glioblastoma tissues and that low expression of LINC00998 was associated with poor prognosis. Overexpression of LINC00998 inhibited glioma cell proliferation in vitro and in vivo and blocked the G1/S cell cycle transition, which exerted a tumor-suppressive effect on glioma progression. Mechanistically, RNA pull-down and mass spectrometry results showed an interaction between LINC00998 and CBX3. IP assays demonstrated that LINC00998 could stabilize CBX3 and prevent its ubiquitination degradation. GSEA indicated that LINC00998 could regulate the c-Met/Akt/mTOR signaling pathway, which was further confirmed by a rescue assay using siRNA-mediated knockdown of CBX3 and the Akt inhibitor MK2206. In addition, dual-luciferase assays showed that miR-34c-5p could directly bind to LINC00998 and downregulate its expression. Our results identified LINC00998 as a novel tumor suppressor in glioma, and LINC00998 could be a novel prognostic biomarker, providing a strategy for precision therapy in glioma patients.Subject terms: Cancer therapy, CNS cancer     

LncRNA PCED1B-AS1 activates the proliferation and restricts the apoptosis of glioma through cooperating with miR-194-5p/PCED1B axis

Glioma with poor prognosis is accepted as a lethal, malignant intracranial tumor among central nervous system diseases. It has been frequently exhibited that long noncoding RNAs (lncRNAs) exert indispensable functions in glioma through regulating gene expression through various molecular mechanisms. To unveil a novel lncRNA functioning in glioma, we browsed the cancer genome atlas dataset and chose the lncRNA PC-esterase domain containing 1B antisense RNA 1 (PCED1B-AS1) for further investigations. Loss-of-function experiments depicted that the proliferation ability was restrained and apoptosis ability was induced in glioma cells by PCED1B-AS1 silencing and this phenomenon was also observed when PCED1B was knocked down. In view of the position of PCED1B-AS1 in the cytoplasm, we produced the Venn diagram and discovered one shared microRNA of PCED1B-AS1 and PCED1B. The competing endogenous RNA network formed by PCED1B-AS1, miR-194-5p, and PCED1B was attested by mechanism assays. Rescue experiments reconfirmed that miR-194-5p suppression or PCED1B overexpression neutralized the obstructive impacts of PCED1B-AS1 silence on proliferation and the promoting effects of PCED1B-AS1 silence on apoptosis. The modulation mechanism of the PCED1B-AS1/miR-194-5p/PCED1B axis in glioma was investigated and affirmed, which supports researchers with a new insight into the therapy of patients with glioma.     

Linc00475 promotes the progression of glioma by regulating the miR-141-3p/YAP1 axis

Glioma is the most prevalent and lethal primary brain tumour. Abundant long non-coding RNAs ( lncRNAs) are aberrant and play crucial roles in the oncogenesis of glioma. The exact functions of linc00475 in glioma remain blurred. Here, we analysed the expression levels of linc00475 by qRT-PCR and discovered that linc00475 was up-regulated in glioma and predicted a poor prognosis in patients with glioma. Besides, inhibiting linc00475 restrained the progression of glioma in vitro and in vivo. Further experiments confirmed that linc00475 regulated the progression of glioma by acting as a sponge for miR-141-3p. Moreover, we detected the binding sites of linc00475 and miR-141-3p, the YAP1- 3′UTR and miR-141-3p by luciferase reporters. The rescue assays confirmed that inhibiting linc00475 restrained the progression of glioma through the miR-141-3p/YAP1 pathway. Collectively, our research demonstrates the key roles of linc00475 in glioma, which could be a promising therapeutic target.     

LncRNA CACNA1G-AS1 facilitates hepatocellular carcinoma progression through the miR-2392/C1orf61 pathway

Emerging studies have indicated that long noncoding RNAs (lncRNAs) possess various functions in initiating human cancers. However, the role of lncRNAs in hepatocellular carcinoma (HCC) still remains ill understood. In this study, we sought to investigate the role of lncRNA CACNA1G-AS1 in HCC progression. Through bioinformatics analysis, we found that CACNA1G-AS1 expression was significantly upregulated in HCC tissues compared with that in the adjacent normal tissues. Moreover, CACNA1G-AS1 upregulation indicated poor prognosis in HCC patients. Knockdown of CACNA1G-AS1 attenuated the proliferation, migration, and invasion of HCC cells. Additionally, decreased expression of CACNA1G-AS1 prevented epithelial–mesenchymal transition. In vivo assay also showed that CACNA1G-AS1 silencing HCC cells have smaller tumor volumes and weights. Further investigations demonstrated that CACNA1G-AS1 worked as a competing endogenous RNA to bind microRNA-2392 (miR-2392) and thereby alleviate the repression of the downstream target C1orf61. Collectively, CACNA1G-AS1 promotes HCC progression through regulating the miR-2392/C1orf61 pathway.