Long non-coding RNA UCA1 promotes malignant phenotypes of renal cancer cells by modulating the miR-182-5p/DLL4 axis as a ceRNA

Abstract

Background: Accumulating literatures have indicated that long non-coding RNAs (lncRNAs) are potential biomarkers that play key roles in tumor development and progression. Urothelial cancer associated 1 (UCA1) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancers. However, the molecular mechanism of UCA1 in renal cancer is still needed to further explore. Methods: The relative expression level of UCA1 was determined by Real-Time qPCR in a total of 88 patients with urothelial renal cancer and in different renal cancer cell lines. Loss-of-function experiments were performed to investigate the biological roles of UCA1 and miR-182-5p on renal cancer cell proliferation, migration, apoptosis and tumorigenicity. Comprehensive transcriptional analysis, dual-luciferase reporter assay and western blot etc. were performed to explore the molecular mechanisms underlying the functions of UCA1. Results: In this study, we found that UCA1 was significantly up-regulated in renal cancer. Moreover, increased UCA1 expression was positively correlated with differentiation and advanced TNM stage. Further experiments demonstrated that knockdown of UCA1 inhibited malignant phenotypes and Notch signal path of renal cancer cells, and miR-182-5p was reverse function as UCA1. UCA1 functioned as a miRNA sponge to positively regulate the expression of Delta-like ligand 4(DLL4) through sponging miR-182-5p and subsequently promoted malignant phenotypes of renal cancer cells, thus UCA1 playing an oncogenic role and miR-182-5p as an antioncogenic one in renal cancer pathogenesis. Conclusion: UCA1-miR-182-5p-DLL4 axis is involved in proliferation and progression of renal cancer. Thus, this study demonstrated that UCA1 plays a critical regulatory role in renal cancer cell and UCA1 may serve as a potential diagnostic biomarker and therapeutic target of renal cancer.

MT1DP loaded by folate-modified liposomes sensitizes erastin-induced ferroptosis via regulating miR-365a-3p/NRF2 axis in non-small cell lung cancer cells

“…The interaction between lncRNAs and miRNA contributes to the occurrence of various diseases 22,23 ; some lncRNAs work as competing endogenous RNAs to regulate target genes 24,25 . In this study, we found that exogenous MT1DP downregulated intracellular miR-365a-3p.…”

Bioinformatics profiling integrating a three immune-related long non-coding RNA signature as a prognostic model for clear cell renal cell carcinoma

“…These findings suggest that the risk evaluating scores based on the three sIRlncRs can contribute to identify the high-risk patients from patients with the same clinical or molecular characteristics, thereby realize individualized and appropriate therapeutic strategy. More recently, Khadirnaikar [26] and Wang [27] et al proposed the prognostic model based on the lncR-SNHG8 and UCA1 in anaplastic gliomas and ccRCC. Chunmi et al highlighted the predicted value of nine IRlncRs (AL138966.2, AL133520.1, AC142472.1, AC127024.5, AC116913.1, AC083880.1, AC124016.1, AC008443.5, and AC092171.5) in pancreatic cancer [28].…”

Long noncoding RNA PICSAR/miR‐588/EIF6 axis regulates tumorigenesis of hepatocellular carcinoma by activating PI3K/AKT/mTOR signaling pathway

“…Accumulating evidence has indicated that lncRNAs modulate target RNA by binding and titrating them off their binding sites on protein‐coding messengers 31,32 . Bioinformatics analysis, luciferase reporter assays, and RNA pull‐down assays revealed that miR‐588 is a target of PICSAR and PICSAR acted as molecular sponge for miR‐588.…”