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Profiling of long non-coding RNAs identifies LINC00958 and LINC01296 as candidate oncogenes in bladder cancer.

ABSTRACT: Aberrant expression of long non-coding RNAs (lncRNAs) has been regarded as a critical component in bladder cancer (BC) and lncRNAs have been associated with BC development and progression although their overall expression and functional significance is still unclear. The aim of our study was to identify novel lncRNAs with a functional role in BC carcinogenesis. RNA-sequencing was used to identify aberrantly expressed lncRNAs in 8 normal and 72 BC samples. We identified 89 lncRNAs that were significantly dys-regulated in BC. Five lncRNAs; LINC00958, LINC01296, LINC00355, LNC-CMC1-1 and LNC-ALX1-2 were selected for further analyses. Silencing of LINC00958 or LINC01296 in vitro reduced both cell viability and migration. Knock-down of LINC00958 also affected invasion and resistance to anoikis. These cellular effects could be linked to direct/indirect regulation of protein coding mRNAs involved in cell death/survival, proliferation and cellular movement. Finally, we showed that LINC00958 binds proteins involved in regulation and initiation of translation and in post-transcriptional modification of RNA, including Metadherin, which has previously been associated with BC. Our analyses identified novel lncRNAs in BC that likely act as oncogenic drivers contributing to an aggressive cancerous phenotype likely through interaction with proteins involved in initiation of translation and/or post-transcriptional modification of RNA.

SUBMITTER: Seitz AK

PROVIDER: S-EPMC5428251 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Profiling of long non-coding RNAs identifies LINC00958 and LINC01296 as candidate oncogenes in bladder cancer.

Seitz Anna Katharina AK Christensen Lise Lotte LL Christensen Emil E Faarkrog Kasper K Ostenfeld Marie Stampe MS Hedegaard Jakob J Nordentoft Iver I Nielsen Morten Muhlig MM Palmfeldt Johan J Thomson Michelle M Jensen Michael Theis Solgaard MT Nawroth Roman R Maurer Tobias T Ørntoft Torben Falck TF Jensen Jørgen Bjerggaard JB Damgaard Christian Kroun CK Dyrskjøt Lars L

Scientific reports 20170324 1

Aberrant expression of long non-coding RNAs (lncRNAs) has been regarded as a critical component in bladder cancer (BC) and lncRNAs have been associated with BC development and progression although their overall expression and functional significance is still unclear. The aim of our study was to identify novel lncRNAs with a functional role in BC carcinogenesis. RNA-sequencing was used to identify aberrantly expressed lncRNAs in 8 normal and 72 BC samples. We identified 89 lncRNAs that were signi ...[more]

PMID: 28341852

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Project description:Background: Increasing evidence shows that dysregulated expression of long non-coding RNAs (lncRNAs) can serve as diagnostic or prognostic markers in bladder cancer. The aim of this study was to evaluate the clinical values of dysregulated lncRNAs in bladder cancer. Methods: Eligible studies were systematically searched in PubMed, Embase, and Web of Science databases from inception to December 2017. Odds ratios (OR) were calculated to investigate the correlation between lncRNAs and clinicopathological parameters. Pooled hazard ratios (HR) and 95% confidence interval (CI) were calculated to explore the prognostic value of lncRNAs in bladder cancer. Pooled diagnostic parameters were also calculated to estimate the performance of lncRNAs in diagnosing bladder cancer. All statistical analyses were performed by using STATA 13.1 program. Results: A total of 37 relevant studies were included to the present systematic review according to the inclusion and exclusion criteria, including 26 on clinicopathological parameters, 19 on prognosis, and 7 on diagnosis. For clinicopathological parameters, MALAT1 expression was significantly associated with lymph node metastasis (OR = 2.731; 95% CI: 1.409-5.292; p = 0.003), and high-level expression of XIST was related to larger tumor size (OR = 2.473; 95% CI: 1.159-5.276; p = 0.019) and higher TNM stage (OR = 0.400; 95% CI, 0.184-0.868; p = 0.020). For the prognostic values, the most significant association was observed between increased expressions of SPRY4-IT1 and poor overall survival (OS) (HR = 3.716; 95% CI: 2.084-6.719; p < 0.001); high MALAT1 expression was significantly associated with poor OS (HR = 1.611; 95% CI: 1.076-2.412; p = 0.020). For the diagnostic values, UCA1 expression profile achieved a combined AUC of 0.92, with sensitivity of 0.84 and specificity of 0.89 in distinguishing patients with bladder cancer from non-cancerous controls. Conclusions: In summary, systematic review elaborated that abnormal lncRNAs expression can serve as potential markers for prognostic evaluation in bladder cancer patients. In addition, the diagnostic meta-analysis concluded that abnormally expressed UCA1 can function as potential diagnostic markers for bladder cancer.

Dataset Information

Profiling of long non-coding RNAs identifies LINC00958 and LINC01296 as candidate oncogenes in bladder cancer.

Publications

Profiling of long non-coding RNAs identifies LINC00958 and LINC01296 as candidate oncogenes in bladder cancer.

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