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Mol Cancer. 2018 Jan 30;17(1):16. doi: 10.1186/s12943-018-0767-3.

Novel evidence for a PIWI-interacting RNA (piRNA) as an oncogenic mediator of disease progression, and a potential prognostic biomarker in colorectal cancer.

Author information

1
Center for Gastrointestinal Research; Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A Sammons Cancer Center, Baylor University Medical Center, 3410 Worth Street, Suite 610, Dallas, TX, 75246, USA.
2
Department of Clinical Laboratory, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China.
3
Center for Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China.
4
Department of Cell Biology; Department of Genetics; Department of Obstetrics, Gynecology, and Reproductive Sciences; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA.
5
Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan.
6
Department of Gastroenterological Surgery and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
7
Department of Pathology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
8
Department of GI Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.
9
Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 20032, China. yanleima@live.cn.
10
Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 20032, China. yanleima@live.cn.
11
Center for Gastrointestinal Research; Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A Sammons Cancer Center, Baylor University Medical Center, 3410 Worth Street, Suite 610, Dallas, TX, 75246, USA. Ajay.Goel@BSWHealth.org.

Abstract

BACKGROUND:

Emerging evidence suggests that PIWI-interacting RNAs (piRNAs) may be important epigenetic regulators of gene expression in human cancers; however, their functional and clinical significance in colorectal cancer (CRC) remains unknown.

METHODS:

We performed piRNA expression profiling in paired cancer and normal tissues through small RNA-sequencing. The clinical significance of candidate piRNAs was investigated, and independently validated in 771 CRC patients from three independent cohorts. The biological function of piRNAs was characterized in cell lines, followed by identification and validation of downstream target genes in CRC tissues.

RESULTS:

We identified piR-1245 as a novel and frequently overexpressed noncoding RNA in CRC, and its expression significantly correlated with advanced and metastatic disease. Patients with high piR-1245 expression experienced significantly shorter overall survival, and multivariate analysis identified its expression to serve as an independent prognostic biomarker in CRC. Functionally, piR-1245 acts as an oncogene and promotes tumor progression, and gene expression profiling results identified a panel of downstream target-genes involved in regulating cell survival pathway. Based upon piRNA:mRNA sequence complementarity, we identified a panel of tumor suppressor genes (ATF3, BTG1, DUSP1, FAS,NFKBIA, UPP1, SESN2, TP53INP1 and MDX1) as direct targets of piR-1245, and successfully validated an inverse correlation between their expression and piR-1245 in CRC.

CONCLUSIONS:

We for the first time have identified the role for a PIWI-interacting noncoding RNA, piR-1245, as a novel oncogene and a potential prognostic biomarker in colorectal cancer.

KEYWORDS:

Biomarker; Colorectal cancer; Noncoding RNA; Oncogene; Prognosis; Tumor suppressor; piR-1245; piRNA

PMID:
29382334
PMCID:
PMC5791351
DOI:
10.1186/s12943-018-0767-3
[Indexed for MEDLINE]
Free PMC Article

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