Long Noncoding RNA <i>PVT1</i> Promotes Non–Small Cell Lung Cancer Cell Proliferation through Epigenetically Regulating LATS2 Expression

111

Background/Aims: Plasmacytoma variant translocation 1 (PVT1) exerts an oncogenic role in many tumors, including lung cancer. However, the roles of PVT1 in regulating radiosensitivity of NSCLC and its underlying mechanism are still unclear. Methods: Expression levels of PVT1 and miR-195 in NSCLC tissues and cells were examined by qRT-PCR. Effects of PVT1 and miR-195 on cell proliferation, apoptosis and colony formation abilities were assessed by MTT assay, flow cytometry and colony formation assay. Luciferase reporter assay was performed to confirm the relationship between PVT1 and miR-195. Tumor xenograft experiments were conducted to observe the effect of PVT1 on radiosensitivity of NSCLC in vivo. Results: PVT1 was negatively correlated with miR-195 expression in NSCLC tissues and associated with poor prognosis of NSCLC patients. Expression of PVT1 and miR-195 varied inversely after irradiation in NSCLC cells. PVT1 knockdown or miR-195 overexpression enhanced radiosensitivity of NSCLC in vitro by inhibiting proliferation and inducing apoptosis. PVT1 directly interacted with miR-195 and regulated its expression. Moreover, PVT1 knockdown improved radiosensitivity of NSCLC cells in vitro and in vivo by sponging miR-195. Conclusion: Knockdown of PVT1 enhances radiosensitivity of NSCLC by sponging miR-195, providing a novel therapeutic target to improve radiotherapy efficiency in NSCLC.

Section: Discussionsupporting

confidence: 91%

Knockdown of Lncrna PVT1 Enhances Radiosensitivity in Non-Small Cell Lung Cancer by Sponging Mir-195

Zhang

et al. 2017

111

“…A meta-analysis by Liu et al also suggested that the up-regulation of PVT1 predicted lymph node metastasis and a worse OS in cancer patients, although the association between PVT1 and other clinicopathological parameters was not discussed [15]_ENREF_15. In addition, other publications since 2015 have continued to investigate the association between PVT1 expression and the prognosis of cancer patients [13, 14, 26-35]. To reach a more convincing conclusion and explore the potential mechanism of action of PVT1 in tumors, we performed the current study by merging the results of published studies and TCGA survival data and conducting GO and KEGG analyses.…”

Section: Discussionmentioning

confidence: 99%

“…In vitro experiments have demonstrated that PVT1 could promote proliferation, migration and invasion of cancer cells. Studies also observed that the level of PVT1 expression was higher in tumor tissues than in adjacent non-cancerous tissues and correlated with a poor prognosis [13, 14]. …”

Section: Introductionmentioning

confidence: 99%

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

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.

“…For example, Wan et al . found that the lncRNA plasmacytoma variant translocation 1 (PVT1) promoted NSCLC proliferation by epigenetically regulating large tumor suppressor kinase 2 (LATS2) expression [10]. LncRNA- urothelial carcinoma-associated 1 (UCA1) exerts oncogenic functions in NSCLC by targeting miR-193a-3p [11].…”

Section: Introductionmentioning

confidence: 99%

The Long Non-Coding RNA XIST Controls Non-Small Cell Lung Cancer Proliferation and Invasion by Modulating miR-186-5p

Wang

Shen

Zhang

et al. 2017

Background/Aims: Long non-coding RNAs (lncRNAs) are key players in the development and progression of human cancers. The lncRNA XIST (X-inactive specific transcript) has been shown to be upregulated in human non-small cell lung cancer (NSCLC); however, its role and molecular mechanisms in NSCLC cell progression remain unclear. Methods: qRT-PCR was conducted to assess the expression of XIST and miR-186. Cell proliferation was detected using MTT assay. Cell invasion and migration were evaluated using transwell assay. Cell cycle distribution and apoptosis rates were analyzed by flow cytometry. Luciferase reporter assay was used to identify the direct regulation of XIST and miR-186. A RNA immunoprecipitation was used to analyze whether XIST was associated with the RNA-induced silencing complex (RISC). Results: We confirmed that XIST was upregulated in NSCLC cell lines and tissues. Functionally, XIST knockdown inhibited cancer cell proliferation and invasion, and induced apoptosis in vitro, and suppressed subcutaneous tumor growth in vivo. Mechanistic investigations revealed a reciprocal repressive interaction between XIST and miR-186-5p. Furthermore, we showed that miR-186-5p has a binding site for XIST. Our data also indicated that XIST and miR-186-5p are likely in the same RNA induced silencing complex. Conclusion: Together, our data revealed that XIST knockdown confers suppressive function in NSCLC and XIST may be a novel therapeutic marker in this disease.