Star-PAP, a poly(A) polymerase, functions as a tumor suppressor in an orthotopic human breast cancer model

Yu, Changqian; Gong, Yingchun; Zhou, Hu; Wang, M; Kong, Lingmei; Liu, J; An, Tao; Zhu, Huarui; Li, Y

doi:10.1038/cddis.2016.199

Cited by 19 publications

(17 citation statements)

References 41 publications

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“…The iSCRIPT cDNA synthesis kit was used to synthesise 300ng of cDNA whereas KAPA Taq PCR was used for reverse transcription PCR (RT-PCR). The real time PCR was achieved by KAPA SYBR FAST qPCR Master Mix (2X) kit from Kapa Biosystems according to the manufacturers' guidelines and the primer sequences for performing both RT-PCR and Real-Time PCR are provided in S3 Table [51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][70][71][72][73][74][75][76]. For each gene, the average C(t) value was determined and was normalised to housekeeping (GAPDH) mRNA levels.…”

Section: Reverse-transcription-pcr and Real-time Pcrmentioning

confidence: 99%

Human papillomavirus E7 binds Oct4 and regulates its activity in HPV-associated cervical cancers

et al. 2020

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Octamer binding transcription factor-4 (Oct4), is highly expressed in stem cells and has indispensable roles in pluripotency and cellular reprogramming. In contrast to other factors used for cellular reprogramming, a role for Oct4 outside embryonic stem cells has been elusive and highly controversial. Emerging evidence implicates Oct4 in the carcinogenic process, but the mechanism through which Oct4 may be functioning in cancers is not fully appreciated. Here, we provide evidence that Oct4 is expressed in human cervical cancer and this expression correlates with the presence of the human papillomavirus (HPV) oncogenes E6 and E7. Surprisingly, the viral oncogenes can complement exogenously provided Oct4 in reprogramming assays, providing functional validation for their ability to activate Oct4 transcription in Mouse Embryonic Fibroblasts (MEFs). To interrogate potential roles of Oct4 in cervical cancers we knocked-down Oct4 in HPV(+) (HeLa & CaSki) and HPV(-) (C33A) cervical cancer cell lines and found that Oct4 knockdown attenuated clonogenesis, only in the HPV(+) cells. More unexpectedly, cell proliferation and migration, were differentially affected in HPV(+) and HPV(-) cell lines. We provide evidence that Oct4 interacts with HPV E7 specifically at the CR3 region of the E7 protein and that introduction of the HPV oncogenes in C33A cells and human immortalised keratinocytes generates Oct4-associated transcriptional and phenotypic patterns, which mimic those seen in HPV(+) cells. We propose that a physical interaction of Oct4 with E7 regulates its activity in HPV(+) cervical cancers in a manner not seen in other cancer types.

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Section: Reverse-transcription-pcr and Real-time Pcrmentioning

confidence: 99%

Human papillomavirus E7 binds Oct4 and regulates its activity in HPV-associated cervical cancers

et al. 2020

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“…Tails, and the enzymes that add them, are critical in a wide spectrum of biological events. For example, uridylation is implicated in tumorigenesis, proliferation, stem cell maintenance, and the immune response 1-10 and regulated poly(A) addition in early development, cancer, and memory [11][12][13][14][15][16][17] . Unbiased and global approaches with single-nucleotide resolution are needed to uncover new types of tails and alternate modification systems that may have gone unnoticed.…”

Section: Introductionmentioning

confidence: 99%

Unbiased screen of RNA tailing enzymes at single-nucleotide resolution reveals a poly(UG) polymerase required for genome integrity and RNA silencing

Preston

Porter

Chen

et al. 2018

Preprint

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Ribonucleotidyl transferases (rNTases) add non-templated ribonucleotides to diverse RNAs. We developed a screening strategy in S. cerevisiae to identify sequences added by candidate enzymes from different organisms at single-nucleotide resolution. The rNTase activities of 19 previously unexplored enzymes were determined. In addition to poly(A)-and poly(U)-adding enzymes, we identified a C-adding enzyme that is likely part of a two-enzyme system that adds CCA to tRNAs in a eukaryote; a nucleotidyl transferase that adds nucleotides to RNA without apparent nucleotide preference; and a poly(UG) polymerase, C. elegans MUT-2, which adds alternating U and G nucleotides to form poly(UG) tails. MUT-2 is known to be required for certain forms of RNA silencing, and mutations in the enzyme that are defective in silencing also fail to add poly(UG) tails in our assay. We propose that MUT-2 poly(UG) polymerase activity is required to promote genome integrity and RNA silencing.

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“…We have established Star-PAP as a negative regulator of cellular invasiveness in breast cancer cells, indicating a putative role of Star-PAP in preventing cancer metastasis. A recent study has shown a role of Star-PAP as a tumor suppressor that prevents cell proliferation by a yet undefined mechanism ( 46 ). Star-PAP antitumor activity was implicated through a previously identified Star-PAP target, the apoptotic BIK gene ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

Nuclear Phosphatidylinositol-Phosphate Type I Kinase α-Coupled Star-PAP Polyadenylation Regulates Cell Invasion

Sudheesh

Laishram

2018

Molecular and Cellular Biology

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Star-PAP, a nuclear phosphatidylinositol (PI) signal-regulated poly(A) polymerase (PAP), couples with type I PI phosphate kinase α (PIPKIα) and controls gene expression. We show that Star-PAP and PIPKIα together regulate 3′-end processing and expression of pre-mRNAs encoding key anti-invasive factors (KISS1R, CDH1, NME1, CDH13, FEZ1, and WIF1) in breast cancer. Consistently, the endogenous Star-PAP level is negatively correlated with the cellular invasiveness of breast cancer cells. While silencing Star-PAP or PIPKIα increases cellular invasiveness in low-invasiveness MCF7 cells, Star-PAP overexpression decreases invasiveness in highly invasive MDA-MB-231 cells in a cellular Star-PAP level-dependent manner. However, expression of the PIPKIα-noninteracting Star-PAP mutant or the phosphodeficient Star-PAP (S6A mutant) has no effect on cellular invasiveness. These results strongly indicate that PIPKIα interaction and Star-PAP S6 phosphorylation are required for Star-PAP-mediated regulation of cancer cell invasion and give specificity to target anti-invasive gene expression. Our study establishes Star-PAP–PIPKIα-mediated 3′-end processing as a key anti-invasive mechanism in breast cancer.

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Star-PAP, a poly(A) polymerase, functions as a tumor suppressor in an orthotopic human breast cancer model

Cited by 19 publications

References 41 publications

Human papillomavirus E7 binds Oct4 and regulates its activity in HPV-associated cervical cancers

Human papillomavirus E7 binds Oct4 and regulates its activity in HPV-associated cervical cancers

Unbiased screen of RNA tailing enzymes at single-nucleotide resolution reveals a poly(UG) polymerase required for genome integrity and RNA silencing

Nuclear Phosphatidylinositol-Phosphate Type I Kinase α-Coupled Star-PAP Polyadenylation Regulates Cell Invasion

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