DOI: 10.1111/cas.12472. Alternative polyadenylation is associated with lower expression of <scp>PABPN</scp>1 and poor prognosis in non‐small cell lung cancer

Alternative polyadenylation is associated with lower expression of PABPN1 and poor prognosis in non‐small cell lung cancer

10.1111/cas.12472

Crossref journal-article

Wiley

Cancer Science (311)

Abstract

Alternative polyadenylation (APA), which induces shortening of the 3′UTR, is emerging as an important phenomenon in gene regulation. APA is involved in development, cancer and cell proliferation. APA may lead to disruption of microRNA‐mediated gene silencing in cancer cells via detachment of microRNA binding sites. We studied the correlation between the APA profile and the tumor aggressiveness in cases of lung cancer. We selected the top 10 genes showing significant 3′UTR shortening in lung cancer, using the package of the Bioconductor for probe‐level analyses of expression microarrays. We established and evaluated the APA score by quantitative RT‐PCR in 147 clinical specimens of non‐small cell lung cancer and compared the results with the clinical outcomes and expression levels of APA‐related genes, including PABPN1, CPEB1, E2F1 and proliferation markers (MKI67, TOP2A and MCM2). High APA scores were correlated with an advanced tumor stage and a poor prognosis (P < 0.001). Multivariate analysis identified the APA score as an independent prognostic factor (hazard ratio, 3.0; P = 0.03). Both lower expression of PABPN1 and higher expression of the proliferation markers were correlated with high APA scores and a poor prognosis, with suppression of PABPN1 exerting its influence independent of gain of the proliferation markers. Moreover, the APA score was correlated with the maximum standardized uptake value of the tumors on positron emission tomography (r = 0.53; P < 0.001). Our results indicate that the loss of PABPN1, a suppressor of APA, might promote tumor aggressiveness by releasing the cancer cells from microRNA‐mediated gene regulation.

Bibliography

Ichinose, J., Watanabe, K., Sano, A., Nagase, T., Nakajima, J., Fukayama, M., Yatomi, Y., Ohishi, N., & Takai, D. (2014). Alternative polyadenylation is associated with lower expression of PABPN1 and poor prognosis in nonâsmall cell lung cancer. Cancer Science, 105(9), 1135â1141. Portico.

Authors 9

Junji Ichinose (first)
Kousuke Watanabe (additional)
Atsushi Sano (additional)
Takahide Nagase (additional)
Jun Nakajima (additional)
Masashi Fukayama (additional)
Yutaka Yatomi (additional)
Nobuya Ohishi (additional)
Daiya Takai (additional)

References 38 Referenced 34

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Dates

Type	When
Created	11 years, 2 months ago (June 28, 2014, 5:45 a.m.)
Deposited	1 year, 11 months ago (Oct. 2, 2023, 10:22 p.m.)
Indexed	4 months, 2 weeks ago (April 17, 2025, 8:04 a.m.)
Issued	11 years ago (Sept. 1, 2014)
Published	11 years ago (Sept. 1, 2014)
Published Online	11 years ago (Sept. 3, 2014)
Published Print	11 years ago (Sept. 1, 2014)

Funders 7

JSPS KAKENHI
Awards1
1. 23390147
JSPS KAKENHI
Awards1
1. 24659267
JSPS KAKENHI
Awards1
1. 25830098
JSPS KAKENHI
Awards1
1. 24791455
JSPS KAKENHI
Awards1
1. 23249045
JSPS KAKENHI
Awards1
1. 22249017
Takeda Science Foundation 10.13039/100007449
Region: Asia
gov (Trusts, charities, foundations (both public and private))
Labels2
1. 公益財団法人　武田科学振興財団
2. TSF

BibTeX

@article{Ichinose_2014, title={Alternative polyadenylation is associated with lower expression of <scp>PABPN</scp>1 and poor prognosis in non‐small cell lung cancer}, volume={105}, ISSN={1349-7006}, url={http://dx.doi.org/10.1111/cas.12472}, DOI={10.1111/cas.12472}, number={9}, journal={Cancer Science}, publisher={Wiley}, author={Ichinose, Junji and Watanabe, Kousuke and Sano, Atsushi and Nagase, Takahide and Nakajima, Jun and Fukayama, Masashi and Yatomi, Yutaka and Ohishi, Nobuya and Takai, Daiya}, year={2014}, month=sep, pages={1135–1141} }

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