LncRNA PANDAR regulates the G1/S transition of breast cancer cells by suppressing p16INK4A expression

Sang, Yi; Tang, Jianjun; Li, Siwei; Li, Liping; Tang, Xiaofeng; Cheng, Chun; Luo, Yanqin; Qian, Xiaohong; Deng, Liang-Ming; Liu, Lijuan; Lv, Xiaobin

doi:10.1038/srep22366

Cited by 58 publications

(64 citation statements)

References 41 publications

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“…A recent study indicated that PANDAR acts as a tumor-promoter in breast cancer by regulating G1/S transition. PANDAR-mediated promotion of cell proliferation occurs via regulation of p16 INK4A 28. In order to understand the biological functions of PANDAR in CCA, we examined the differences in cell proliferation after suppressing PANDAR expression by using CCK-8 and colony formation assays.…”

Section: Discussionmentioning

confidence: 99%

Upregulated long noncoding RNA PANDAR predicts an unfavorable prognosis and promotes tumorigenesis in cholangiocarcinoma

Jiang

Cui

2017

OTT

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Cholangiocarcinoma (CCA) is one of the most malignant human cancers with increasing incidence worldwide. LncRNAs have emerged as gene regulators and prognostic biomarkers in a variety of neoplasms. PANDAR, a novel cancer-related lncRNA, has been reported to be upregulated in diverse human carcinomas. In this study, we aimed to investigate the clinical significance of lncRNA PANDAR in CCA and explore its functional roles in CCA cells including cell proliferation, apoptosis, migration, invasion and epithelial-to-mesenchymal transition (EMT). The results showed that PANDAR was significantly upregulated in CCA tissue specimens and cell lines, and its high expression was closely associated with lymph node invasion (P=0.004), TNM stage (P=0.034) and postoperative relapse (P=0.006) in patients with CCA. Thus, overexpression of PANDAR could serve as an independent prognostic biomarker of CCA. Furthermore, silencing of PANDAR followed by siRNA significantly inhibited cell proliferation and increased apoptosis in CCA cells. In addition, suppression of PANDAR impaired migration and invasion capacity in vitro partly by affecting EMT. Overall, our findings showed that lncRNA PANDAR serves as a novel prognostic biomarker and therapeutic target for CCA.

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Section: Discussionmentioning

confidence: 99%

Upregulated long noncoding RNA PANDAR predicts an unfavorable prognosis and promotes tumorigenesis in cholangiocarcinoma

Jiang

Cui

2017

OTT

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“…It has been demonstrated that various transcription factors, such as Ets and Bmi1, play critical roles in the transcriptional regulation p16 gene5. Our earlier studies showed that the histone acetyltransferase p300 recruited by Sp1 stimulated p16 transcription through inducing the H4 hyperacetylation on p16 gene, whereas HDAC3/4 inhibited the p16 promoter activity via the transcription factors YY1 and ZBP-89678.…”

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confidence: 95%

The interplay between p16 serine phosphorylation and arginine methylation determines its function in modulating cellular apoptosis and senescence

Yang

et al. 2017

Sci Rep

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Cyclin-dependent kinase inhibitor p16INK4a (p16) primarily functions as a negative regulator of the retinoblastoma protein (Rb) -E2F pathway, thus plays critical role in cell cycle progression, cellular senescence and apoptosis. In this study, we showed that the methylation of Arg 138 and the phosphorylation of Ser 140 on p16 were critical for the control of cell proliferation and apoptosis. Compared to wild type p16, mutant p16R138K possessed improved function in preventing cell proliferation and inducing apoptosis, while the Ser 140 mutation (p16S140A) exhibited the opposite alteration. We also demonstrated that H2O2 was able to induce the phosphorylation of p16, which facilitated the interaction between CDK4 (Cyclin-dependent protein kinase) and p16, in 293T (human emborynic kidney) cells. Furthermore, the elevated arginine methylation in p16S140A mutant and increased serine phosphorylation in p16R138K mutant suggest that a antagonizing mechanism coordinating Arg 138 methylation and Ser 140 phosphorylation to regulates p16 function as well as cellular apoptosis and senescence. These findings will therefore contribute to therapeutic treatment for p16-related gene therapy by providing theoretical and experimental evidence.

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“…It is induced during DNA damage in a p53-dependent manner and inhibits the expression of apoptotic genes [19]. Aberrant PANDAR expression is reported in a variety of human cancers, including bladder cancer, breast cancer, osteosarcoma etc [20][21][22][23]. It exerts numerous molecular functions, such as promoting cell proliferation, invasion, epithelial-mesenchymal transition and metastasis, besides, it can suppress tumor cell apoptosis [20][21][22][23][24][25].…”

Section: Meta-analysismentioning

confidence: 99%

The value of long noncoding RNA PANDAR as a biomarker of prognosis in carcinomas: a meta-analysis

Yan¹,

Zhu²,

Li³

et al. 2018

Oncotarget

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Promoter of CDKN1A antisense DNA damage activated RNA (PANDAR) has been demonstrated to be aberrantly expressed in various types of cancer and might be serve as a potential biomarker for human cancers. The present study conducted a meta-analysis to investigate whether the expression of lncRNA PANDAR was associated with prognosis and clinicopathological features in relevant cancers. 10 eligible studies with a total of 1211 patients were collected by searching the electronic bibliographic databases, the results show that high expression level of PANDAR could significantly predict shorter OS in cancer patients (HR = 2.08, 95% CI: 1.55-2.80, P < 0.001) except in patients with non-small cell lung cancer (NSCLC). There was also a significant association between high level of PANDAR and advanced TNM stage (OR = 2.80, 95% CI = 1.57-4.99, P < 0.001), positive lymph node metastasis (OR = 2.92, 95% CI = 1.92-4.45, P < 0.001), larger tumor size (OR = 1.41, 95% CI = 1.04-1.89, P = 0.03) and poor tumor differentiation (OR = 1.53, 95% CI = 1.09-2.15, P = 0.01). In conclusion, the meta-analysis results indicate that increased expression level of PANDAR was associated with unfavorable prognosis and might serve as a predictive factor for advanced clinicopathological features in various cancers.

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LncRNA PANDAR regulates the G1/S transition of breast cancer cells by suppressing p16INK4A expression

Cited by 58 publications

References 41 publications

Upregulated long noncoding RNA PANDAR predicts an unfavorable prognosis and promotes tumorigenesis in cholangiocarcinoma

Upregulated long noncoding RNA PANDAR predicts an unfavorable prognosis and promotes tumorigenesis in cholangiocarcinoma

The interplay between p16 serine phosphorylation and arginine methylation determines its function in modulating cellular apoptosis and senescence

The value of long noncoding RNA PANDAR as a biomarker of prognosis in carcinomas: a meta-analysis

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