Long Non-coding RNAs in Urologic Malignancies: Functional Roles and Clinical Translation

Chen, Jiajia; Miao, Zhijun; Xue, Boxin; Shan, Yuxi; Weng, Guobin; Shen, Bairong

doi:10.7150/jca.15876

Cited by 38 publications

(21 citation statements)

References 130 publications

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“…Owing to the high recurrence and heterogeneity of this disease, the characterization of the molecular profile of tumors and investigating putative biomarkers is imperative. A number of molecules, including microRNA (miRNA), long chain non-coding RNAs and other RNAs, have been demonstrated to be associated with the occurrence and development of bladder cancer, and the underlying molecular mechanisms and prognostic features have been analyzed extensively (4).…”

Section: Introductionmentioning

confidence: 99%

circLPAR1 is a novel biomarker of prognosis for muscle‑invasive bladder cancer with invasion and metastasis by miR‑762

et al. 2019

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Circular RNAs (circRNAs) are a specific form of non-coding RNAs, that serve a pivotal role in the development of human diseases, including Alzheimer's disease and cancer; however, only a few are known with respect to cancer. The present study identified a novel circRNA, circ lysophosphatidic acid receptor 1 (LPAR1) (hsa_circ_0087960), derived from two exons 226 base pairs in length, in muscle-invasive bladder cancer (MIBC) tissues. circLPAR1 was identified to be lowly expressed in MIBC tissues in a cohort of 125 cases, and predicted a poor disease-specific survival time, compared with patients with high circLPAR1 expression (52.4 vs. 56.0 months; P=0.001) by univariate and multivariate Cox regression analyses. Matrigel and wound healing assays also demonstrated that the invasion of 5637 and T24 bladder cancer cells were significantly enhanced following the knockdown of circLPAR1 by small interfering RNA (si-circLPAR1-1 in T24 cell line, P= 0.01; si-circLPAR1-2 in 5637 cell line, P= 0.003; si-circLPAR1-2 in T24 cell line, P= 0.002; si-circLPAR1-2 in 5637 cell line, P= 0.006). The bioinformatics analysis indicated that circLPAR1 may harbor specific microRNAs (miRNAs) according to the miRNAs seed sequence matching. A luciferase reporter assay revealed that miR-762 can inhibit the activity of the transfected luciferase gene when inserted in a circLPAR1 wild-type fragment, and this inhibition could be alleviated when the luciferase gene was inserted in a circLPAR1 fragment with the mutated miR-762 target site. In conclusion, the circLPAR1 may function as a potential novel and stable biomarker for the prognosis of MIBC and may be associated with the invasion and metastasis by miR-762.

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Section: Introductionmentioning

confidence: 99%

circLPAR1 is a novel biomarker of prognosis for muscle‑invasive bladder cancer with invasion and metastasis by miR‑762

et al. 2019

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“…The ncRNAs are classified according to their size in nucleotides (nt) into small-ncRNAs (sncRNA <200 nt) and long-ncRNAs (lncRNA >200 nt) [ 3 ]. Much effort has been spent to identify and functionally characterize dysregulated microRNAs [ 4 , 5 ] and lncRNAs [ 6 ] in BCA in the past years, but few is known about other subtypes of the ncRNAs. YRNAs (Ro-associated Y) were recognized as a component of soluble ribonucleoproteins (Ro RNPS) in the blood of patients with rheumatic autoimmune diseases [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

YRNA expression predicts survival in bladder cancer patients

et al. 2017

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BackgroundNon-coding RNAs play an important role in human carcinogenesis. YRNAs (Ro-associated Y), a novel class of non-coding RNAs, have been identified as biomarker in various malignancies, but remain to be studied in urinary bladder cancer (BCA) patients.MethodsThe expression of all four YRNAs (RNY1, RNY3, RNY4, RNY5) was determined in archival BCA (urothelial carcinoma, n = 88) and normal urothelial bladder (n = 30) tissues using quantitative real-time PCR. Associations with clinicopathological parameters and prognostic role for overall and cancer-specific survival were analysed.ResultsAll YRNAs were significantly downregulated in BCA tissue. A low expression of RNY1, RNY3 and RNY4 was associated with muscle-invasive BCA, lymph node metastases and advanced grade. Furthermore, expression of RNY1 and RNY3 was predictive for BCA patients’ overall (also RNY4) and cancer-specific survival as estimated using Kaplan-Meier and univariate (but not multivariate) Cox regression analyses. RNY1, RNY3 and RNY4 show good discriminative ability between tumor and normal tissue, as well as between muscle-invasive and non-muscle-invasive urothelial carcinoma.ConclusionsThe expression of YRNAs is altered in BCA and associated with poor prognosis. Possible diagnostic role of YRNAs should be investigated in further studies.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3746-y) contains supplementary material, which is available to authorized users.

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“…lncRNAs are found in sense or antisense orientation for protein-coding genes, within introns of protein-coding genes or intergenic regions of the genome (9). Though small non-coding RNAs (<200 bp), particularly miRNAs (21-23 nucleotides), are well characterized as post-transcriptional regulators of mRNAs and their roles in cancer are well established (10,11), lncRNAs are still under investigation and more information is needed to understand the role of lncRNAs in cancer occurrence and progression (12).…”

Section: Introductionmentioning

confidence: 99%

Knockdown of DUXAP10 inhibits proliferation and promotes apoptosis in bladder cancer cells via PI3K/Akt/mTOR signaling pathway

Chen

et al. 2017

Int J Oncol

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DUXAP10 is a member of long non-coding RNAs (lncRNAs) and has been reported to be upregulated in bladder cancer (BC) tissues. However, the biological functions of DUXAP10 in BC are largely unknown. The present study detected the expression of DUXAP10 in human normal bladder cell SV‑HUC‑1 and BC cell lines. Subsequently, cell proliferation, cell cycle, and apoptosis were analyzed by knockdown of the DUXAP10 expression. Results suggested that the expression level of DUXAP10 was significantly enhanced in cancer cells. After knockdown of DUXAP10, cell proliferation was inhibited, cell cycle was arrested at G0/G1 phase, and apoptosis was increased in T24 and 5637 cells. Western blot analysis detected that knockdown of DUXAP10 decreased the expression of Bcl-xL, cyclin D and CDK4. This increased the expression of Bad, cleaved caspase‑3, cleaved caspase-9, and p27. Further studies indicated that knockdown of DUXAP10 inhibited PI3K/Akt/mTOR signaling pathway. Combining these results, our study suggests that DUXAP10 plays an important role in BC and DUXAP10 inhibition is a potential therapeutic target for BC.

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Long Non-coding RNAs in Urologic Malignancies: Functional Roles and Clinical Translation

Cited by 38 publications

References 130 publications

circLPAR1 is a novel biomarker of prognosis for muscle‑invasive bladder cancer with invasion and metastasis by miR‑762

circLPAR1 is a novel biomarker of prognosis for muscle‑invasive bladder cancer with invasion and metastasis by miR‑762

YRNA expression predicts survival in bladder cancer patients

Knockdown of DUXAP10 inhibits proliferation and promotes apoptosis in bladder cancer cells via PI3K/Akt/mTOR signaling pathway

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