Mechanism Of Urothelial Carcinoma-associated 1 Research Articles

LncRNA UCA1 promotes development of gastric cancer via the miR-145/MYO6 axis

BackgroundLong noncoding RNA (lncRNA), urothelial carcinoma-associated 1 (UCA1) is aberrantly expressed in multiple cancers and has been verified as an oncogene. However, the underlying mechanism of UCA1 in the development of gastric cancer is not fully understood. In the present study, we aimed to identify how UCA1 promotes gastric cancer development.MethodsThe Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to analyze UCA1 and myosin VI (MYO6) expression in gastric cancer. Western blot and quantitative real-time PCR (QPCR) were performed to test the expression level of the UCA1/miR-145/MYO6 axis in gastric cancer cell lines and tissues. The roles of the UCA1/miR-145/MYO6 axis in gastric cancer in vitro and in vivo were investigated by CCK-8 assay, flow cytometry, siRNAs, immunohistochemistry, and a mouse xenograft model. The targeted relationship among UCA1, miR-145, and MYO6 was predicted using LncBase Predicted v.2 and TargetScan online software, and then verified by luciferase activity assay and RNA immunoprecipitation.ResultsUCA1 expression was higher but miR-145 expression was lower in gastric cancer cell lines or tissues, compared to the adjacent normal cell line or normal tissues. Function analysis verified that UCA1 promoted cell proliferation and inhibited cell apoptosis in the gastric cancer cells in vitro and in vivo. Mechanistically, UCA1 could bind directly to miR-145, and MYO6 was found to be a downstream target gene of miR-145. miR-145 mimics or MYO6 siRNAs could partly reverse the effect of UCA1 on gastric cancer cells.ConclusionsUCA1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-145 to upregulate MYO6 expression in gastric cancer, indicating that the UCA1/miR-145/MYO6 axis may serve as a potential therapeutic target for gastric cancer.

Silencing of UCA1 Protects Against MPP+-Induced Cytotoxicity in SK-N-SH Cells via Modulating KCTD20 Expression by Sponging miR-423-5p.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. Long noncoding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been implicated in PD development. Nevertheless, little insight has been gained on the mechanisms of UCA1 in PD pathogenesis. The levels of UCA1, miR-423-5p and potassium channel tetramerization domain containing 20 (KCTD20) were assessed by qRT-PCR and western blot. Cell viability was gauged by the CCK-8 assay, and cell apoptosis was detected by flow cytometry. Targeted relationships among UCA1, miR-423-5p and KCTD20 were verified by dual-luciferase reporter and RNA immunoprecipitation assays. Our data showed that MPP+ induced UCA1 expression in SK-N-SH cells. UCA1 silencing protected against MPP+-evoked cytotoxicity in SK-N-SH cells. UCA1 functioned as a miR-423-5p sponge, and the protective impact of UCA1 silencing on MPP+-evoked cytotoxicity was mediated by miR-423-5p. KCTD20 was a direct target of miR-423-5p, and miR-423-5p overexpression mitigated MPP+-triggered cell injury by down-regulating KCTD20. Furthermore, UCA1 regulated KCTD20 expression by acting as a sponge of miR-423-5p in SK-N-SH cells. Our study first identified that the silencing of UCA1 protected SK-N-SH cells from MPP+-evoked cytotoxicity at least in part by targeting the miR-423-5p/KCTD20 axis.

Long Noncoding RNA UCA1 Facilitates Endometrial Cancer Development by Regulating KLF5 and RXFP1 Gene Expressions.

Objective: Long noncoding RNA urothelial carcinoma associated 1 (UCA1) was found to facilitate endometrial cancer cell metastasis, and high UCA1 expression predicted endometrial cancer development and patients' worsened outcomes. This research aimed to investigate the cancer promoting role and mechanism of UCA1 in endometrial cancer. Materials and Methods: Around 64 endometrioid adenocarcinoma patients' tissue specimens were analyzed by qRT-PCR. Primary endometrial cancer cell culture was established in vitro. UCA1 overexpression or knockdown was executed by adenoviral transduction. Cell proliferation, apoptosis, colony formation, transwell invasion, and epithelia-to-mesenchymal transition of primary endometrial cancer cells were assessed. Interactions among UCA1, microRNAs (miRNAs), and mRNAs were investigated by luciferase reporter assay and argonaute 2 (AGO2)-RNA immunoprecipitation. Nude mouse xenograft assay was used to explore the role of UCA1 in endometrial cancer in vivo. Results: UCA1 was significantly upregulated in endometrial cancer tissues compared to normal tissues. High expression of UCA1 associated with endometrial cancer progression and patients' decreased survival. Overexpressing UCA1 significantly increased the malignancy of primary endometrial cancer cells in vitro, while UCA1 knockdown showed opposite effect. Kruppel-like factor 5 (KLF5) and relaxin like family peptide receptor 1 (RXFP1) were found as two UCA1 co-expressing genes in endometrial cancer. UCA1 increased the malignancy of endometrial cells partially through KLF5, and it increased the relaxin 2-induced endometrial cancer cell metastasis through RXFP1. UCA1 reduced the si-RNA-induced silencing of KLF5 and RXFP1 genes in endometrial cancer cells. MiR-143-3p and miR-1-3p were found to interact with both UCA1 and KLF5 mRNA. In addition, knockdown of UCA1 suppressed tumor growth in endometrial cancer in vivo. Conclusion: UCA1 might facilitate endometrial cancer development by upregulating KLF5 and RXFP1 gene expression by sponging miR-143-3p and miR-1-3p.

Long non-coding RNA UCA1 modulates cell proliferation and apoptosis by regulating miR-296-3p/Myc axis in acute myeloid leukemia

ABSTRACT Acute myeloid leukemia (AML) is a common hematopoietic malignancy with a generally poor prognosis. Long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been identified as an oncogene in various malignancies including AML. However, the role and mechanisms of UCA1 in AML tumorigenesis were incompletely understood. Hence, this study aims to investigate whether UCA1 regulates AML progression by miR-296-3p/Myc axis. Cell proliferation and apoptosis were evaluated by MTT assay and flow cytometry, respectively. Luciferase reporter assay was performed to analyze the interaction between miR-296-3p and UCA1 or Myc. The results showed that UCA1 knockdown inhibited proliferation and induced apoptosis in AML cells (U937 and HL60). Mechanistically, UCA1 acted as a sponge of miR-296-3p by binding to miR-296-3p. Myc, a target of miR-296-3p, was positively regulated by UCA1. Functional assay showed that the anti-AML effect of UCA1 knockdown could be abrogated by miR-296-3p inhibition and Myc overexpression. Moreover, UCA1 knockdown inhibited AML cell tumorigenesis in vivo, which was associated with regulation of miR-296-3p and Myc expression. In conclusion, UCA1 modulates AML progression by regulating miR-296-3p/Myc axis.

Long non-coding RNA UCA1 promotes autophagy by targeting miR-96-5p in acute myeloid leukaemia.

Long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been identified as an oncogene and is involved in acute myeloid leukaemia (AML). Autophagy contributes to tumourigenesis and cancer cell survival. The purpose of this study was to investigate the regulatory role and mechanism of UCA1 in AML cell viability by its effect on autophagy. The expression of UCA1, miR-96-5p, and ATG7 was determined by qRT-PCR and western blot. Cell proliferation was examined by MTT assay. The autophagy level was assessed by green fluorescent protein (GFP)-LC3 immunofluorescence and western blot. The interaction between UCA1 and miR-96-5p or ATG7 was analyzed by luciferase reporter activity. The results showed that UCA1 promoted AML cell proliferation by inducing autophagy. Mechanistically, UCA1 acted as a sponge of miR-96-5p by binding to miR-96-5p. ATG7 was a direct target of miR-96-5p and positively regulated by UCA1. Further results showed that the miR-96-5p mimic effectively counteracted the UCA1 overexpression-mediated induction of the ATG7/autophagy pathway. Collectively, UCA1 functions as a sponge of miR-96-5p to upregulate its target ATG7, thereby resulting in autophagy induction. Our findings reveal a UCA1-mediated molecular mechanism responsible for autophagy induction in AML and help to improve the understanding of the molecular mechanism of AML progression.

LncRNA-UCA1 modulates progression of colon cancer through regulating the miR-28-5p/HOXB3 axis.

Emerging evidence has shown that the long noncoding RNA urothelial carcinoma-associated 1 (UCA1) plays a tumor-promoting role in colorectal cancer, while miR-28-5p shows tumor-inhibitory activity in several tumor types. However, the mechanisms both of these in colon cancer progression are still unknown. In this work, the detailed roles and mechanisms of UCA1 and its target genes in colon cancer were studied. The results showed that UCA1 was upregulated in colon cancer tissues when compared with the adjacent nonhumorous tissues, as well as in the various colon cancer cell lines, but the expression of miR-28-5p showed an opposite trend. Furthermore, a high UCA1 level in colon cancer tissues is positively associated with the tumor size and advanced tumor stages. Functional assays revealed that both UCA1 knockdown and miR-28-5p overexpression could inhibit colon cancer cell growth and migration. Further mechanistic studies indicated that UCA1 knockdown played tumor suppressive roles in SW480 and HT116 cells through binding with miR-28-5p. We also, for the first time, identified HOXB3 as the target gene of miR-28-5p and that HOXB3 overexpression could mediate the functions of UCA1 in cell proliferation and migration of colon cancer cells. In conclusion, our data provided evidence for the regulatory network of UCA1/miR-28-5p/HOXB3 in colon cancer, suggesting that UCA1, miR-28-5p, and HOXB3 are the potential targets for colon cancer therapy.

Expression and mechanism of UCA1 in gastrointestinal tumors

Urothelial carcinoma associated 1 (UCA1) is a kind of long non-coding RNA (lncRNA), which has no capacities for coding proteins. UCA1 over-expresses in diverse tumors, and plays a pivotal role in initiation and progression of tumors. Researches indicate that UCA1 may function as an oncogene in gastrointestinal tumors, such as gastric cancer, colorectal cancer and hepatocellular cancer, and participate in regulating cell proliferation, metastasis and chemo-resistance. Key words: Gastrointestinal neoplasms; Long non-coding RNA; Urothelial carcinoma associated 1