Effects of lncRNA-UCA1 targeting miR-204-5p on the proliferation, migration, apoptosis and immune escape of endometrial carcinoma cells / 中华肿瘤杂志

Objective: To investigate the effect of long non-coding RNA urothelial carcinoma-associated 1 (UCA1) gene on the proliferation, migration, apoptosis and immune escape of endometrial cancer cells and its molecular mechanism. Methods: Endometrial cancer tissues and adjacent normal tissues of patients with endometrioid adenocarcinoma who underwent total or partial hysterectomy in Henan Provincial People's Hospital from 2017 to 2019 were collected. The expressions of UCA1 and miR-204-5p were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and the cell proliferation, migration and apoptosis were detected by cell counting kit 8 (CCK8) method, Transwell method, flow cytometry, and dual-luciferase reporter assay was used to explore the target relationship between UCA1 and miR-204-5p. HEC-1A-sh-NC or HEC-1A-sh-UCA1 cells were co-cultured with peripheral blood mononuclear cells (PBMC) or cytokine-induced killer cells in vitro to explore the role of UCA1 in immune escape. Results: The expression level of UCA1 in endometrial cancer tissue (17.08±0.84) was higher than that in adjacent normal endometrial tissue (3.00±0.37), and the expression level of miR-204-5p (0.98±0.16) was lower than that in adjacent normal endometrial tissue (2.00±0.20, P<0.05). Pearson correlation analysis showed that the expression of miR-204-5p was negatively correlated with the expression of UCA1 (r=-0.330, P=0.030). The expressions of UCA1 and miR-204-5p were associated with the International Federation of Gynecology and Obstetrics stage of endometrial cancer, lymph node metastasis and vascular invasion (P<0.05). The relative ratio of absorbance (0.58±0.11) and the number of cell migration [(199.68±18.44)] in the sh-UCA1 group were lower than those in the sh-NC group (1.24±0.17 and 374.76±24.83), respectively. The apoptosis rate of sh-UCA1 group [(28.64±7.80)%] was higher than that of sh-NC group [(14.27±4.38)%, P<0.05]. After different ratios of effector cells and target cells were cultured, the cell survival rate of HEC-1A-sh-UCA1 group was lower than that of HEC-1A-sh-NC group, and the difference was statistically significant (P<0.05). UCA1 had a binding site for miR-204-5p. The relative ratio of absorbance (1.74±0.08) and the number of cell migration (426.00±18.00) cells in the UCA1+ anti-miR-204-5p group were higher than those in the control group [1.00±0.03 and (284.00±8.00) cells, respectively]. The apoptosis rate of UCA1+ anti-miR-204-5p group [(5.42±0.93)%] was lower than that of control group [(14.82±1.48)%, P<0.05]. HEC-1A-sh-UCA1 cells could induce higher interferon gamma (IFN-γ) expression when co-cultured with PBMC, and the levels of IFN-γ expression in PHA group and PHA+ pre-miR-204-5p group cells were 2.42±0.49 and 1.88±0.26, which were higher than that in the PHA+ pre-NC group (0.85±0.10, P<0.05). When co-cultured with cytokine-induced killer cells (different ratios) in vitro, the HEC-1A-sh-UCA1 group and the HEC-1A-pre-miR-204-5p group had lower survival rates than that in the HEC-1A-pre-miR-204-5p group. In the HEC-1A-pre-NC group, the differences were statistically significant (P<0.05). Conclusion: UCA1/miR-204-5p may play an important role in human endometrial cancer.

The expression of lncRNA UCA1 and its role on the proliferation and invasion in hepatic cancer and HepG2 cells / 天津医药

@# Objective Toinvestigatetheeffectsoflongnon-codingRNAurothelialcarcinoma-associated1(lncRNA UCA1) silencing on cell proliferation and invasion of human hepatic cancer HepG2 cells, and its mechanism thereof. Methods TheexpressionoflncRNAUCA1wasanalyzedbyreal-timePCRin20tumortissueand20adjacentnon-tumor tissuesamplesofhepaticcancer.HepG2cellswasculturedin vitro,andlncRNAUCA1specificshorthairpinRNA(shRNA1 andshRNA2)wastransfected.CCK-8assay,TranswellassayandWound-healingassaywereusedtodetecttheeffectof lncRNAUCA1silencingoncellproliferation,invasionandmigrationofHepG2cells.TheeffectoflncRNAUCA1silencing onproteinandmRNAexpressionofCyclinD1,vascularendothelialgrowthfactor(VEGF),matrixmetalloproteinase(MMP)9,focaladhesionkinase(FAK)andIntegrinβ3onlncRNAUCA1silencingwasmeasuredbyreal-timePCRandWestern blotassay.Results TheexpressionofLncRNAUCA1washigherinhepaticcancertissues.ThesilencingoflncRNAUCA1 significantly inhibited the growth of HepG2 cells, and the abilities of cell invasion and migration were downregulated. Westernblotassayandreal-timePCRshowedthatexpressionsofCyclinD1,VEGF,MMP-9,FAKandIntegrinβ3were significantlyinhibited.Conclusion TheresultssuggestthattheabnormalexpressionoflncRNAUCA1isassociatedwith thedevelopmentofhumanhepaticcancer.ThesilencingoflncRNAUCA1couldsuppressthecellproliferation,invasionand migrationofhepaticcarcinomacells.

Expression and mechanism of UCA1 in gastrointestinal tumors / 国际肿瘤学杂志

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.

Advances of long non-coding RNA UCA1 in cancers / 国际肿瘤学杂志

Long non-coding RNA urothelial carcinoma associated 1 (UCA1) is initially discovered and named in bladder cancer tissue,which is highly expressed in multi types of tumor tissues,such as bladder cancer,ovarian cancer,lung cancer,suggesting that UCA1 acts as oncogene.UCA1 is confirmed to regulate tumor cell proliferation,apoptosis,invasion and migration,which plays an important role in the occurrence and development of cancers.UCA1 is expected to become a new biomarker for diagnosis,prognosis and drug susceptibility,which may be a promising therapeutic target of cancer.

Expression of long non-coding RNA UCA1 and miR-34b in bladder cancer and analysis of clinic-pathologic correlation / 中华泌尿外科杂志

Objective To study the expression of long non-coding RNA (lncRNA)-urothelial carcinoma associated 1 (UCA1) and miR-34b in bladder cancer and its correlation to the clinicopathologic features of bladder cancer.Methods Between January 2011 and October 2012,the expression of UCA1 and miR-34b in 5 bladder cancer cell lines (T24,BIU-87,EJ,T24-MMC,T24-ADM) and 1 normal bladder cell lines (SV-HUC-1) were measured by real-time reverse transcription-polymerase chain reaction (RTPCR).Meanwhile,the 56 bladder cancer specimens and paraneoplastic normal bladder tissues,which diagnosed by pathology were collected from bladder cancer patients undergoing radical resection of bladder.Among them,41 cases were male and 15 cases were female.The mean age was (68.4 ± 7.5)years old,range 52 to 78 years.43 cases were older than 65 years old,and 13 cases were less than 65 years old.The pathological classification included non muscle-invasive bladder cancer (NMIBC) 18 cases,muscle-invasive bladder cancer 38 cases;low grade papillary urothelial carcinoma 22 cases,high grade papillary urothelial carcinoma 34 cases;12 cases were primary lesion,the other 44 cases were diagnosed as tumor recurrence.Real-time RT-PCR was performed to analyze the expression of UCA1 and miR-34b.Results The relative expression levels of UCA1 in the normal bladder cell lines (SV-HUC-1) and 5 bladder cancer cell lines (T24,BIU-87,EJ,T24-MMC and T24-ADM) were (0.0675 ± 0.0133),(0.2934 ± 0.0531),(0.4246 ± 0.0650),(0.4206 ± 0.0826),(0.6472 ± 0.0875) and (0.7165 ± 0.1032),respectively (P ＜ 0.05).Moreover,the expression levels of UCA1 were up-regulated in 2 drug resistant bladder cancer cells lines T24-MMC (0.6472 ± 0.0875)and T24-ADM (0.7165 ± 0.1032),as compared with the T24 bladder cancer lines (0.2934 ± 0.0531),respectively (P ＜ 0.05).However,the expression levels of miR-34b in 5 bladder cancer cell lines [T24 (0.1600 ± 0.0455),BIU-87 (0.1720 ± 0.0658),EJ (0.1150 ± 0.0352),T24-MMC(0.0576 ± 0.0087),T24-ADM (0.0510 ± 0.0125)] were decreased (P ＜ 0.05),as compared with normal bladder cell lines SV-HUC-1 (0.6384 ± 0.1083).Moreover,the expression levels of miR-34b were down-regulated in 2 drug resistant bladder cancer cells lines T24-MMC (0.0576 ± 0.0087) and T24-ADM(0.0510 ± 0.0125),as compared with the T24 bladder cancer lines T24 (0.1600 ± 0.0455),respectively (P ＜ 0.05).The relative expression levels of UCA1 and miR-34b in bladder cancer tissues and paraneoplastic normal bladder tissues were (0.4225 ± 0.0714) vs.(0.0532 ± 0.0192) and (0.0340 ± 0.0134)vs.(0.5643 ±0.0616),respectively (P ＜0.05).Statistical correlation analysis showed that UCA1 to be significantly negative correlated with miR-34b in bladder cancer specimens(r =-0.54,P ＜ 0.05).The high level of UCA1 and low level of miR-34b were significantly correlated with tumor malignant grade,invasiveness and recurrence.The 3-year overall survival rate (OS) in UCA1 (+)/miR-34b(-) group (27.6％) were significantly worse compared with non UCA1 (+)/miR-34b (-) group (73.7％).Conclusion High expression of UCA1 and low expression of miR-34b were associated with the occurrence and development of bladder cancer.

Effect of long non-coding RNA UCA1 on invasion and metastasis of pancreatic cancer cell lines / 基础医学与临床

Objective To explore the expression of urothelial carcinoma-associated 1 ( UCA1 ) in pancreatic cancer cell lines and its influence on the invasion and metastasis of the pancreatic cancer cells .Methods The expression of UCA1 in pancreatic cancer tissues and paired adjacent normal tissues ( 11 cases ) and 5 pancreatic cancer cell lines was analyzed by real-time PCR.The level of UCA1 in BxPC-3 was knocked down by small interfering RNA . The ability of invasion and migration in vitro of transfected BxPC-3 was detected by Transwell invasion assay and wound healing assay .The protein levels of MMP-2 and MMP-9 were measured by Western blot experiment .Results The expression level of UCA1 in pancreatic cancer tissues was higher than that in paired adjacent normal tissues , and UCA1 differentially expressed in 5 pancreatic cancer cell lines .Down-regulation of UCA1 by siRNA suppressed the expression of MMP-2 and MMP-9 in BxPC3, and dramatically impaired the ability of invasion and migration of BxPC-3.Conclusions UCA1 is over-expressed in pancreatic cancer , and down-regulation of UCA1 attenuates the capacity of invasion and metastasis in vitro of BxPC-3 by decreasing MMP-2 and MMP-9.