Tetracycline-inducible shRNA targeting long non-coding RNA PVT1 inhibits cell growth and induces apoptosis in bladder cancer cells

Zhuang, Cheng‐Le; Li, Jianfa; Liu, Yuchen; Chen, Mingwei; Yuan, Jiancheng; Fu, Xing; Zhan, Yonghao; Liu, Li; Lin, Junhao; Zhou, Qing; Xu, Wen; Zhao, Guoping; Cai, Zhiming; Huang, Weiren

doi:10.18632/oncotarget.5880

Cited by 76 publications

(70 citation statements)

References 31 publications

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“…Studies have shown that the level of PVT1 expression was clearly up-regulated in cancer tissues compared with paired adjacent tissues [31, 38-41], The same result was also detected in cell line samples in vitro [34, 42]. In recent years, studies on the mechanism of action of PVT1 in cancer have proliferated, and increasing evidence suggested that PVT1 could affect diverse biological behaviors of multiple tumors.…”

Section: Discussionmentioning

confidence: 81%

Prognostic Significance of LncRNA PVT1 and Its Potential Target Gene Network in Human Cancers: a Comprehensive Inquiry Based Upon 21 Cancer Types and 9972 Cases

Qin

Lin

et al. 2018

Cell Physiol Biochem

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Background/Aims: Whether the level of long noncoding RNA plasmacytoma variant translocation 1 gene (lncRNA PVT1) expression influences the clinical development and outcome of human cancers has not been thoroughly elucidated to date. Inconsistencies still exist regarding the associations between PVT1 and the clinicopathological features, including patient survival data. Additionally, the regulatory mechanism of PVT1 among human cancers remains unclear. Methods: we conducted a comprehensive inquiry to verify the implication of PVT1 expression in cancer patients by conducting a meta-analysis of 19 selected studies and The Cancer Genome Atlas (TCGA) database to examine the relationship between PVT1 expression and both the prognosis and clinicopathological features of cancer patients using STATA 12.0. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the potential mRNA target genes of PVT1 gathered from TANRIC and Multi Experiment Matrix (MEM) were performed. Results: The level of PVT1 expression in tumor tissues was higher than in paired non-cancer tissues and was significantly associated with a poorer prognosis in cancer patients. Additionally, overexpression of PVT1 was significantly correlated with histological differentiation, tumor (T) classification, lymph node (N) classification and TNM stages. Furthermore, a total of 462 validated target genes were identified, and the GO and KEGG analyses demonstrated that the validated targets of PVT1 were significantly enriched in several pathways, including the GnRH signaling pathway, the Cytokine-cytokine receptor interaction pathway, the Inflammatory mediator regulation of TRP channels pathway, and the Neuroactive ligand-receptor interaction pathway. Conclusion: PVT1 may serve as a potential biomarker associated with the progression and prognosis of human cancers.

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Section: Discussionmentioning

confidence: 81%

Prognostic Significance of LncRNA PVT1 and Its Potential Target Gene Network in Human Cancers: a Comprehensive Inquiry Based Upon 21 Cancer Types and 9972 Cases

Qin

Lin

et al. 2018

Cell Physiol Biochem

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“…Accumulating evidences suggest that long non-coding RNAs (lncRNAs) perform important functions in regulation of genes which control tumor proliferation, apoptosis, and migration, and stretched our understanding of the biological behavior in diseases especially in carcinomas including bladder cancer [23][24][25][26][27][28][29].Furthermore, these previous study indicate that lncRNAs are valuable biomarkers and therapeutic targets [28,[30][31][32][33]. The antisense Long non-coding RNA HIF1A-AS2 was located in chromosome 14q23.2, and has been found to be overexpressed in tumor tissues, such as chronic myeloid leukemia and neuroblastoma [34].HIF1A-AS2 is upregulated in gastric cancer Page 18 of 28 and knockdown of HIF1A-AS2 expression by siRNA could inhibit cell proliferation in vitro and tumorigenesis in vivo [12].…”

Section: Discussionmentioning

confidence: 99%

“…In the past several years, medical synthetic biology utilizing the principles of engineering has made many remarkable achievements for treating human diseases including bladder cancer [16,30,[35][36][37]. Inspired by the engineering principles of synthetic biology and these previously productive works, we designed the tetracycline-inducible switch and measured its cancer inhibition effects in bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

Tetracycline-inducible shRNA targeting antisense long non-coding RNA HIF1A-AS2 represses the malignant phenotypes of bladder cancer

et al. 2016

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Various studies have indicated that long non-coding RNAs (lncRNAs) play vital roles in the cancer development and progression. LncRNA hypoxia inducible factor 1alpha antisense RNA-2 (HIF1A-AS2) is upregulated in gastric carcinomas and knockdown of HIF1A-AS2 expression by siRNA could inhibit cell proliferation in vitro and tumorigenesis in vivo. Inspired by these observations, we hypothesized that HIF1A-AS2 possibly plays the analogous roles in bladder cancer. In our study, we first reported that HIF1A-AS2 was up-regulated in bladder cancer tissues and cells, and HIF1A-AS2 expression level in bladder cancer tissues is positively associated with advanced clinical pathologic grade and TNM phase. Cell proliferation inhibition, cell migration suppression and apoptosis induction were observed by silencing HIF1A-AS2 in bladder cancer T24 and 5637 cells. Overexpression of HIF1A-AS2 in SV-HUC-1 cells could promote cell proliferation, cell migration and anti-apoptosis. Besides, we utilized the emerging technology of medical synthetic biology to design tetracycline-inducible small hairpin RNA (shRNA) vector which specifically silenced HIF1A-AS2 in a dosage-dependent manner to inhibit the progression of human bladder cancer. In conclusion, our data suggested that HIF1A-AS2 plays oncogenic roles and can be used as a therapeutic target for treating human bladder cancer. Synthetic "tetracycline-on" switch system that quantitatively controlled the expression of HIF1A-AS2 in bladder cancer can inhibit the progression of bladder cancer cells in a dosage-dependent manner. Our findings provide new insights into the role of the lncRNA HIF1A-AS2 in the bladder cancer.

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“…With the identification of long non-coding RNAs (lncRNAs), it has been demonstrated that certain lncRNAs may serve important roles in BC (5,(7)(8)(9)(10). LncRNAs are a category of non-coding RNAs, containing >200 nucleotides with limited translation potential.…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA HNF1A-AS1 promotes cell viability and migration in human bladder cancer

Zhang

Wang

2018

Oncol Lett

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Abstract. Bladder cancer is among the most frequent types of genitourinary malignancies and results in high morbidity and mortality. Despite considerable progress in methods of bladder cancer diagnosis and treatment, the detailed underlying molecular mechanisms of bladder cancer remain unclear, and the prognosis of patients remains poor. In the present study, the role of long non-coding (lnc)RNA hepatocyte nuclear factor 1A (HNF1A)-antisense RNA (AS)1 in bladder cancer progression was examined in vitro. HNF1A-AS1 was overexpressed in clinical bladder cancer tissues and cultured bladder cancer cells. Specific short hairpin RNAs against HNF1A-AS1 knocked down the expression of HNF1A-AS1, and thus suppressed the viability and migration/invasion abilities of the cells. Additionally, the depletion of HNF1A-AS1 in bladder cancer T24 and 5637 cell lines also induced cell accumulation in G 0 /G 1 phase with the cell cycle analysis. Overall, these data suggest that lncRNA HNF1A-AS1 may be a potential regulator of bladder cancer tumorigenesis, and provide novel insight into the diagnosis and treatment of bladder cancer. IntroductionBladder cancer (BC) has the second most frequent incidence of cancers of the genitourinary tract worldwide (1). In 2012 alone, 430,000 incident patients with BC and 165,000 BC-associated mortalities were identified (1). Although advances in treatment have been made in previous decades, the recurrence rate of BC is between 15 and 90% within 5 years, and the 5-year-survival-rate is ~75% (2-5). In total, ~15% of patients with papillary BC develop muscle-invasive and metastatic cancer (3). In these patients, long-term medical care is required, with inevitably high personnel and socioeconomic cost (6). Therefore, it is important to identify novel clues to diagnose and treat BC.With the identification of long non-coding RNAs (lncRNAs), it has been demonstrated that certain lncRNAs may serve important roles in BC (5,7-10). LncRNAs are a category of non-coding RNAs, containing >200 nucleotides with limited translation potential. Unlike other non-coding RNAs, including microRNAs, the underlying molecular mechanisms of different lncRNAs involved in human diseases remain largely unknown. To date, lncRNAs have been demonstrated to participate in multiple intracellular and extracellular activities, including gene transcription, mRNA splicing and tumorigenesis (11)(12)(13)(14)(15). For example, the dysregulation of lncRNAs has been demonstrated in different types of cancer including hepatocellular carcinoma-upregulated lncRNA in hepatocellular carcinoma (16), metastasis-associated lung adenocarcinoma transcript 1 in lung cancer (17) and urothelial cancer-associated 1 and ZEB2 natural antisense transcript in BC (18,19).Unfortunately, despite the increasing implications of lncRNAs in bladder tumorigenesis, no lncRNA has been widely recognized as a specific biomarker for the progression or prognosis of BC. This fact, to a certain extent, encourages focus on novel lncRNAs in BC. Hepatocyte nuclear factor 1A (HNF...

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Tetracycline-inducible shRNA targeting long non-coding RNA PVT1 inhibits cell growth and induces apoptosis in bladder cancer cells

Cited by 76 publications

References 31 publications

Prognostic Significance of LncRNA PVT1 and Its Potential Target Gene Network in Human Cancers: a Comprehensive Inquiry Based Upon 21 Cancer Types and 9972 Cases

Prognostic Significance of LncRNA PVT1 and Its Potential Target Gene Network in Human Cancers: a Comprehensive Inquiry Based Upon 21 Cancer Types and 9972 Cases

Tetracycline-inducible shRNA targeting antisense long non-coding RNA HIF1A-AS2 represses the malignant phenotypes of bladder cancer

Long non-coding RNA HNF1A-AS1 promotes cell viability and migration in human bladder cancer

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