A serum-circulating long noncoding RNA signature can discriminate between patients with clear cell renal cell carcinoma and healthy controls

Long non-coding RNAs (lncRNAs), a class of non-coding transcripts, have recently been emerging with heterogeneous molecular actions, adding a new layer of complexity to generegulation networks in tumorigenesis. LncRNAs are considered important factors in several ovarian cancer histotypes, although few have been identified and characterized. Owing to their complexity and the lack of adapted molecular technology, the roles of most lncRNAs remain mysterious. Some lncRNAs have been reported to play functional roles in ovarian cancer and can be used as classifiers for personalized medicine. The intrinsic features of lncRNAs govern their various molecular mechanisms and provide a wide range of platforms to design different therapeutic strategies for treating cancer at a particular stage. Although we are only beginning to understand the functions of lncRNAs and their interactions with microRNAs (miRNAs) and proteins, the expanding literature indicates that lncRNA-miRNA interactions could be useful biomarkers and therapeutic targets for ovarian cancer. In this review, we discuss the genetic variants of lncRNAs, heterogeneous mechanisms of actions of lncRNAs in ovarian cancer tumorigenesis, and drug resistance. We also highlight the recent developments in using lncRNAs as potential prognostic and diagnostic biomarkers. Lastly, we discuss potential approaches for linking lncRNAs to future gene therapies, and highlight future directions in the field of ovarian cancer research.

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Long Non-Coding RNAs: the New Horizon of Gene Regulation in Ovarian Cancer

Worku

Bhattarai

Ayers

et al. 2017

“…Numerous studies have reported that lncRNAs could be crucial players in cancer progression, particularly in terms of dysregulation of gene products that contribute to advanced human tumors [5][6][7]. Furthermore, lncRNAs could also be considered as diagnostic or prognostic markers due to their clinical association with tumor outcomes [8][9][10]. More recently, Pandolfi et al proposed a new regulatory mechanism in which all RNA transcripts harboring miRNA-binding sites can communicate and regulate each other's expression levels by competing specifically for shared miRNAs, thus acting as competing endogenous RNAs (ceRNAs) [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Upregulation of MIAT Regulates LOXL2 Expression by Competitively Binding MiR-29c in Clear Cell Renal Cell Carcinoma

Qü¹,

Xiao²,

Xiao³

et al. 2018

Background/Aims: MIAT is a long noncoding RNA (lncRNA) involved in cell proliferation and the development of tumor. However, the exact effects and molecular mechanisms of MIAT in clear cell renal cell carcinoma (ccRCC) progression are still unknown. Methods: We screened the lncRNAs’ profile of ccRCC in The Cancer Genome Atlas database, and then examined the expression levels of lncRNA MIAT in 45 paired ccRCC tissue specimens and in cell lines by q-RT-PCR. MTS, colony formation, EdU, and Transwell assays were performed to examine the effect of MIAT on proliferation and metastasis of ccRCC. Western blot and luciferase assays were performed to determine whether MIAT can regulate Loxl2 expression by competitively binding miR-29c in ccRCC. Results: MIAT was up-regulated in ccRCC tissues and cell lines. High MIAT expression correlated with worse clinicopathological features and shorter survival rate. Functional assays showed that knockdown of MIAT inhibited renal cancer cell proliferation and metastasis in vitro and in vivo. Luciferase and western blot assays further confirmed that miR-29c binds with MIAT. Additionally, the correlation of miR-29c with MIAT and Loxl2 was further verified in patients' samples. Conclusion: Our data indicated that MIAT might be an oncogenic lncRNA that promoted proliferation and metastasis of ccRCC, and could be a potential therapeutic target in human ccRCC.

“…The past decade has witnessed the discovery of diverse IncRNAs involved in physiological and pathological processes [8-12]. Many IncRNAs have been reported as important regulators in ccRCC, and several were also verified as biomarkers for early diagnosis and prognostic prediction for ccRCC [13, 14]. …”

Section: Introductionmentioning

confidence: 99%

LINC00037 Inhibits Proliferation of Renal Cell Carcinoma Cells in an Epidermal Growth Factor Receptor-Dependent Way

Gong

et al. 2018

Background/Aims: LINC00037 has previously been reported to be up-regulated in clear cell renal cell carcinoma (ccRCC), however, the underlying mechanism remained unknown. In this study, we designed to investigate the functional role of LINC00037 in ccRCC Methods: LINC00037 knockdown and re-expressing 786-O and A498 cells were established. CCK8 assay and EdU assay were performed to evaluate the proliferation rates of ccRCC cells. Flow cytometry assay was performed to detect the cell apoptosis and cell cycle. Subcutaneous injection xenotransplantation mouse model was used to observe the role of LINC00037 in tumor growth in vivo. Mass spectrometry (MS) was performed to find the interacting partner of LINC00037 and RNA immunoprecipitation (RIP) was carried out to validate their interaction. Results: We found that knockdown of LINC00037 resulted in inhibited cell proliferation with activated apoptosis and cell cycle arrest in vitro. Over-expression of LINC00037 in LINC00037 knockdown cells restored and enhanced cell proliferation. In vivo mouse model indicated reduced tumor progression by LINC00037 depletion and promoted tumor progression by LINC00037 overexpression. LINC00037 could bind to epidermal growth factor receptor (EGFR) and increase the protein level of EGFR. Conclusion: LINC00037 could inhibit proliferation of ccRCC in an epidermal growth factor receptor-dependent way.