Theophylline controllable RNAi-based genetic switches regulate expression of lncRNA TINCR and malignant phenotypes in bladder cancer cells

Chen, Zhicong; Liu, Yuchen; He, Anbang; Li, Jianfa; Chen, Mingwei; Zhan, Yonghao; Lin, Junhao; Zhuang, Cheng‐Le; Liu, Li; Zhao, Guoping; Huang, Weiren; Cai, Zhiming

doi:10.1038/srep30798

Cited by 44 publications

(37 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 8 Moreover, Zhang et al suggested that TINCR expression was obviously reduced in colorectal cancer tissues and cell lines compared with their counterparts. 15 However, there was more evidence suggesting that TINCR was overexpressed in human cancers including hepatocellular carcinoma, 16 bladder cancer, 17 breast cancer, 18 esophageal cancer 19 and gastric cancer. 20 , 21 In addition, the expression status of TINCR in lung cancer is still controversial.…”

Section: Discussionmentioning

confidence: 99%

LncRNA TINCR is associated with clinical progression and serves as tumor suppressive role in prostate cancer

Dong¹,

Ding²,

Li³

et al. 2018

CMAR

View full text Add to dashboard Cite

IntroductionTerminal differentiation-induced non-coding RNA (TINCR) has been suggested to have aberrant expression in multiple human cancers, and functions as tumor suppressor or promoter in various types of human tumors depending on the specific cancer types. The expression status and biological function of TINCR in prostate cancer is still unknown.Materials and methodsIn our study, we detected TINCR expression in prostate cancer tissue samples and cell lines, and analyzed the association between TINCR expression and clinical parameters in 160 prostate cancer patients. Moreover, we conducted gain-of-function and loss-of-function studies in prostate cancer cell to explore the biological function and molecular mechanism of TINCR.ResultsIn our results, low-expression TINCR was observed in prostate cancer, and correlated with advanced clinical T stage, lymph node involvement, distant metastasis, high Gleason score and poor prognosis in prostate cancer patients. Moreover, levels of TINCR expression were negatively associated with TRIP13 mRNA and protein expressions in prostate cancer tissues, and negatively regulated the TRIP13 mRNA and protein expressions in prostate cancer cell lines. TINCR inhibits prostate cancer cell proliferation, migration and invasion via suppressing TRIP13 expression.ConclusionTINCR plays a tumor suppressive role in regulating prostate cancer cell proliferation, migration and invasion through modulating TRIP13 expression.

show abstract

Section: Discussionmentioning

confidence: 99%

LncRNA TINCR is associated with clinical progression and serves as tumor suppressive role in prostate cancer

Dong¹,

Ding²,

Li³

et al. 2018

CMAR

View full text Add to dashboard Cite

show abstract

“…They do not encode proteins, but play important roles in regulating gene expression through both epigenetic and posttranscriptional mechanisms 6 . Although little is known about the carcinogenic mechanisms of lncRNAs, many lncRNAs have been found to be abnormally expressed in bladder cancer 7 , including UCA1 (urothelial carcinoma associated) 8 , HOTAIR (HOX transcript antisense intergenic RNA) 9 and TINCR (tissue differentiation-inducing non-protein coding RNA) 10 .Yet, the biological roles of lncRNAs in bladder cancers are largely unknown. Metastasis associated lung adenocarcinoma transcript 1(MALAT1) is a long non-coding RNA that is upregulated in many cancers, such as breast, pancreatic, lung, colon, prostate and liver cancer 4 .…”

Section: Introductionmentioning

confidence: 99%

LncRNA MALAT1 Inhibits Apoptosis and Promotes Invasion by Antagonizing miR-125b in Bladder Cancer Cells

et al. 2017

Self Cite

View full text Add to dashboard Cite

Accumulating evidences suggest that longnon-coding RNAs (lncRNAs) play functional roles in development of different cancers, including cancer initiation and progression. Metastasis associated lung adenocarcinoma transcript 1(MALAT1) is a well-known lncRNA which was previously shown to be a direct target of miR-125b in bladder cancer (BCa) and to promote cancer progression and invasion. However, little is known whether MALAT1 can also target miR-125b. In the present study, using CRISPR-based technologies and qRT-PCR, we show that MALAT1 is capable of suppressing mature miR-125b and increasing the expression of its target genes (Bcl-2 and MMP-13), but has no effect on pri-miR-125b and pre-miR-125b. We observe that the biotin-labeled MALAT1-RNA probe is able to pull down Ago2 and miR-125b and that the negative regulation of miR-125b by MALAT1 is dependent on Ago2. Importantly, the results of flow cytometry assay and transwell assay reveal that the MALAT1-mediated cancer progression is in part due to specific suppression of miR-125b and activation of its two target genes. All together, these data suggest that the “MALAT1-miR-125b-Bcl-2 / MMP-13” axis plays an important role in the progression of BCa, thereby may provide a potential therapeutic strategy for the treatment of human BCa.

show abstract

“…In addition, Zhang et al revealed that downregulation of TINCR promoted proliferation and metastasis in colorectal cancer and TINCR could be considered as a potential cancer suppressor gene [ 11 ]. Furthermore, Chen et al demonstrated that TINCR could promote bladder cancer development and progression and TINCR knockdown might provide a novel therapeutic strategy for bladder cancer [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

LncRNA TINCR attenuates cardiac hypertrophy by epigenetically silencing CaMKII

Shao

Chen

et al. 2017

Oncotarget

View full text Add to dashboard Cite

In the previous study, we established a mouse model of cardiac hypertrophy using transverse aortic constriction (TAC) and found that the expression of long non-coding RNAs TINCR was downregulated in myocardial tissue. The present study was designed to determine the potential role of TINCR in the pathogenesis of cardiac hypertrophy. Our results showed that enforced expression of TINCR could attenuate cardiac hypertrophy in TAC mice. Angiotensin II (Ang-II) was found to be associated with reduced TINCR expression and increased hypertrophy in cultured neonatal cardiomyocytes. RNA-binding protein immunoprecipitation assay confirmed that TINCR could directly bind with EZH2 in cardiomyocytes. The results of chromatin immunoprecipitation assay revealed that EZH2 could directly bind to CaMKII promoter region and mediate H3K27me3 modification. Knockdown of TINCR was found to reduce EZH2 occupancy and H3K27me3 binding in the promoter of CaMKII in cardiomyocytes. In addition, enforced expression of TINCR was found to decrease CaMKII expression and attenuate Ang-II-induced cardiomyocyte hypertrophy. Furthermore, our results also showed that Ang-II could increase CaMKII expression in cardiomyocytes, which consequently contributed to cellular hypertrophy. In conclusion, our findings demonstrated that TINCR could attenuate myocardial hypertrophy by epigenetically silencing of CaMKII, which may provide a novel therapeutic strategy for cardiac hypertrophy.

show abstract

Theophylline controllable RNAi-based genetic switches regulate expression of lncRNA TINCR and malignant phenotypes in bladder cancer cells

Cited by 44 publications

References 42 publications

LncRNA TINCR is associated with clinical progression and serves as tumor suppressive role in prostate cancer

LncRNA TINCR is associated with clinical progression and serves as tumor suppressive role in prostate cancer

LncRNA MALAT1 Inhibits Apoptosis and Promotes Invasion by Antagonizing miR-125b in Bladder Cancer Cells

LncRNA TINCR attenuates cardiac hypertrophy by epigenetically silencing CaMKII

Contact Info

Product

Resources

About