OIP5 Promotes Growth, Metastasis and Chemoresistance to Cisplatin in Bladder Cancer Cells.

Opa interacting protein 5 (OIP5) has previously been identified as a tumorigenesis gene. The purpose of this study is to explore the role of OIP5 in the progression of bladder cancer (BC). The OIP5 expression and clinical behaviors in bladder cancer were collected from lager database. Our study showed that OIP5 was highly expressed in bladder cancer tissues and cells. Overexpression of OIP5 in tumor patients predicted worse overall survival (OS) and higher histological grade. Vitro and vivo experiments demonstrated that knockdown of OIP5 significantly inhibited cell growth of BC. Scratch assay and transwell assay suggested that migration capacity of BC cells was decreased after knockdown of OIP5. Cisplatin sensitivity assay indicated that depletion of OIP5 increased the sensitivity of BC cells to cisplatin. Finally, we identified 38 overlapping differentially expressed genes (DEGs) between RNA-seq and TCGA analyses which were closely linked to OIP5. Bioinformatics analysis showed that these DEGs enriched in oocyte meiosis, fanconi anemia pathway, cell cycle, and microRNAs regulation. TOP2A, SPAG5, SKA1, EXO1, TK1 were confirmed to associated with bladder cancer development. Our study suggests that OIP5 may be a potential biomarker for growth, metastasis and drug-resistance in bladder cancer.

The Function and Mechanism of Long Non-coding RNA-ATB in Cancers.

Long non-coding RNAs (lncRNAs) are a class of transcriptional RNA molecules with a length of greater than 200 nucleotides that function as regulatory factors in many human diseases. Studies have shown that lncRNAs are involved in multiple cellular processes, including proliferation, apoptosis, migration, and invasion. In this report, a long non-coding RNA-ATB that is overexpressed in various tumor tissues and cell lines was investigated. Recent evidence suggests that ATB is dysfunctional in a variety of cancers, including hepatocellular carcinoma, gastric cancer (GC), colorectal cancer (CRC), breast cancer (BC), prostate cancer, renal cell carcinoma, non-small cell lung cancer (NSCLC), pancreatic cancer, osteosarcoma, and glioma. The high expression of ATB is associated with clinicopathological features of cancer patients. In addition, overexpression of lncRNA-ATB can promote tumor proliferation, migration, and invasion. LncRNA-ATB induces epithelial-mesenchymal transition (EMT) by competitively binding to miRNAs, thus promoting tumor progression. Biological functions and mechanisms of ATB in human cancers are discussed here, concluding that lncRNA-ATB may provide a new biomarker for use in diagnosis and prognosis of cancer.

Synthetic artificial "long non-coding RNAs" targeting oncogenic microRNAs and transcriptional factors inhibit malignant phenotypes of bladder cancer cells.

Both oncogenic transcription factors (TFs) and microRNAs (miRNAs) play important roles in human cancers, acting as transcriptional and post-transcriptional regulators, respectively. These phenomena raise questions about the ability of an artificial device to simultaneously regulate miRNAs and TFs. In this study, we aimed to construct artificial long non-coding RNAs, "alncRNAs", and to investigate their therapeutic effects on bladder cancer cell lines. Based on engineering principles of synthetic biology, we combined tandem arrayed aptamer cDNA sequences for TFs with tandem arrayed cDNA copies of binding sites for the miRNAs to construct alncRNAs. In order to prove the utility of this platform, we chose ß-catenin and the miR-183-182-96 cluster as the functional targets and used the bladder cancer cell lines 5637 and SW780 as the test models. Dual-luciferase reporter assay, real-time quantitative PCR (qRT-PCR) and related phenotypic experiments were used to test the expression of related genes and the therapeutic effects of our devices. The result of dual-luciferase reporter assay and qRT-PCR showed that alncRNAs could inhibit transcriptional activity of TFs and expression of corresponding microRNAs. Using functional experiments, we observed decreased cell proliferation, increased apoptosis, and motility inhibition in alncRNA-infected bladder cancer cells. What's more, follow-up mechanism experiments further confirmed the anti-tumor effect of our devices. In summary, our synthetic devices indeed function as anti-tumor regulators, which synchronously accomplish transcriptional and post-transcriptional regulation in bladder cancer cells. Most importantly, anti-cancer effects were induced by the synthetic alncRNAs in the bladder cancer lines. Our devices, all in all, provided a novel strategy and methodology for cancer studies, and might show a great potential for cancer therapy if the challenges of in vivo DNA delivery are overcome.

AFAP1-AS1: A novel oncogenic long non-coding RNA in human cancers.

Long non-coding RNAs (lncRNAs), a group of non-protein-coding RNAs with more than 200 nucleotides in length, are involved in multiple biological processes, such as the proliferation, apoptosis, migration and invasion. Moreover, numerous studies have shown that lncRNAs play important roles as oncogenes or tumour suppressor genes in human cancers. In this paper, we concentrate on actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1), a well-known long non-coding RNA that is overexpressed in various tumour tissues and cell lines, including oesophageal cancer, pancreatic ductal adenocarcinoma, nasopharyngeal carcinoma, lung cancer, hepatocellular carcinoma, ovarian cancer, colorectal cancer, biliary tract cancer and gastric cancer. Moreover, high expression of AFAP1-AS1 was associated with the clinicopathological features and cancer progression. In this review, we sum up the current studies on the characteristics of AFAP1-AS1 in the biological function and mechanism of human cancers.

Long non-coding PANDAR as a novel biomarker in human cancer: A systematic review.

OBJECTIVES: Long non-coding RNAs (lncRNAs) are characterized as a group of RNAs that more than 200 nucleotides in length and have no protein-coding function. More and more evidences provided that lncRNAs serve as key molecules in the development of cancer. Deregulation of lncRNAs functions as either oncogenes or tumour suppressor genes in various diseases. Recently, increasing studies about PANDAR in cancer progression were reported. In our review, we will focus on the current research on the character of PANDAR include the clinical management, tumour progression and molecular mechanisms in human cancers. MATERIALS AND METHODS: We summarize and analyze current studies concerning the biological functions and mechanisms of lncRNA PANDA in tumour development. The related studies were obtained through a systematic search of Pubmed. RESULTS: PANDAR was a well-characterized oncogenic lncRNA and widely overexpressed in many tumours. PANDAR is upregulated in many types of cancer, including colorectal cancer, lung cancer, renal cell carcinoma, cholangiocarcinoma, osteosarcoma, thyroid cancer and other cancers. Upregulation of PANDAR was significantly associated with advanced tumour weights, TNM stage and overall survival. Furthermore, repressed of PANDAR would restrain proliferation, migration and invasion. CONCLUSION: PANDAR may act as a powerful tumour biomarker for cancer diagnosis and treatment.

BANCR: a novel oncogenic long non-coding RNA in human cancers.

Long non-coding RNAs account for large proportion of non-coding transcripts in human genomes. Though they lack of open reading framework and cannot encode protein, they can control endogenous gene expression though regulating cell life activities. They serve as transcriptional modulator, posttranscriptional processor, chromatin remodeler and splicing regulator during the process of gene modification. Moreover, long non-coding RNAs were regarded as potential tumor markers for cancer diagnosis and prognosis. BANCR was identified as a cancer-promoting long non-coding RNA in melanoma tissues. Since then, increasing studies about BANCR in cancer progression were reported. BANCR was dysregulated in various cancers including melanoma, colorectal cancer, retinoblastoma, lung carcinoma and hepatocellular carcinoma, and increased BANCR expression cause poor prognosis and shorter survival rate of cancer patients. Furthermore, the functions and mechanisms of BANCR in cancer cells have been clarified. Here, we focus on the current research on the role of BANCR in the clinical management, progression and molecular mechanisms in human cancer.

LncRNA MALAT1 Inhibits Apoptosis and Promotes Invasion by Antagonizing miR-125b in Bladder Cancer Cells.

Accumulating evidences suggest that longnon-coding RNAs (lncRNAs) play functional roles in development of different cancers, including cancer initiation and progression. Metastasis associated lung adenocarcinoma transcript 1(MALAT1) is a well-known lncRNA which was previously shown to be a direct target of miR-125b in bladder cancer (BCa) and to promote cancer progression and invasion. However, little is known whether MALAT1 can also target miR-125b. In the present study, using CRISPR-based technologies and qRT-PCR, we show that MALAT1 is capable of suppressing mature miR-125b and increasing the expression of its target genes (Bcl-2 and MMP-13), but has no effect on pri-miR-125b and pre-miR-125b. We observe that the biotin-labeled MALAT1-RNA probe is able to pull down Ago2 and miR-125b and that the negative regulation of miR-125b by MALAT1 is dependent on Ago2. Importantly, the results of flow cytometry assay and transwell assay reveal that the MALAT1-mediated cancer progression is in part due to specific suppression of miR-125b and activation of its two target genes. All together, these data suggest that the "MALAT1-miR-125b-Bcl-2 / MMP-13" axis plays an important role in the progression of BCa, thereby may provide a potential therapeutic strategy for the treatment of human BCa.

Colon cancer associated transcripts in human cancers.

Long non-coding RNAs serve as important regulators in complicated cellular activities, including cell differentiation, proliferation and death. Dysregulation of long non-coding RNAs occurs in the formation and progression of cancers. The family of colon cancer associated transcripts, long non-coding RNAs colon cancer associated transcript-1 and colon cancer associated transcript-2 are known as oncogenes involved in various cancers. Colon cancer associated transcript-1 is a novel lncRNA located in 8q24.2, and colon cancer associated transcript-2 maps to the 8q24.21 region encompassing rs6983267. Colon cancer associated transcripts have close associations with clinical characteristics, such as lymph node metastasis, high TNM stage and short overall survival. Knockdown of them can reverse the malignant phenotypes of cancer cells, including proliferation, migration, invasion and apoptosis. Moreover, they can increase the expression level of c-MYC and oncogenic microRNAs via activating a series of complex mechanisms. In brief, the family of colon cancer associated transcripts may serve as potential biomarkers or therapeutic targets for human cancers.