Quercetin 3,3',4',7-O-tetramethyl ether; Quercetin 3,7,3',4'-tetramethyl ether; Retusine
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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.
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.
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.
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.
Electronic supplementary material
The online version of this article (10.1186/s12943-018-0767-3) contains supplementary material, which is available to authorized users.
Colorectal cancer, piRNA, piR-1245, Prognosis, Biomarker, Noncoding RNA, Tumor suppressor, Oncogene
Novel evidence for a PIWI-interacting RNA (piRNA) as an oncogenic mediator of disease progression, and a potential prognostic biomarker in colorectal cancer
Wenhao Weng,#1,2,3 Na Liu,#4 Yuji Toiyama,5 Masato Kusunoki,5 Takeshi Nagasaka,6 Toshiyoshi Fujiwara,6 Qing Wei,7 Huanlong Qin,8 Haifan Lin,4 Yanlei Ma,corresponding author9,10 and Ajay Goelcorresponding author1
Emerging reports demonstrated that PIWI‐interacting RNAs (piRNAs) played an indispensable role in tumorigenesis. However, it still remains elusive whether piR‐1245 in gastric juice specific in stomach could be employed as a biomarker for gastric cancer (GC). The present work is aiming at exploring the possibility of piR‐1245 in gastric juice as a potential marker to judge for diagnosis and prognosis of gastric cancer.
Gastric juice was collected from 66 GC patients and 66 healthy individuals. Quantitative real‐time reverse transcriptase polymerase chain reaction (qRT‐PCR) was employed to measure the levels of piR‐1245 expression. Then, the pattern of piR‐1245 expression in gastric juice was determined between GC patients and healthy individuals. A receiver operating characteristic (ROC) curve was constructed for distinguishing GC from healthy individuals.
Gastric juice piR‐1245 levels in GC were higher than those of controls (P < .0001). The value of area under ROC (AUC) was 0.885 (sensitivity, 90.9%; specificity, 74.2%; 95% confidence interval, 0.8286 to 0.9414). High gastric juice piR‐1245 expression was signally correlated with tumor size (P = .013) and TNM stage (P = .001). GC patients with high piR‐1245 expression in gastric juice exerted a poorer overall survival (OS) (P = .0152) and progression‐free survival (PFS) (P = .013). COX regression analysis verified that gastric juice piR‐1245 expression was an independent prognostic risk variable for OS (P < .05). Conclusions The current study suggested that piR‐1245 in gastric juice had the potential to be a useful biomarker for GC detection and prognosis prediction.
biomarker, gastric cancer, gastric juice, piR‐1245, PIWI‐interacting RNA
Gastric juice piR‐1245: A promising prognostic biomarker for gastric cancer
Xiaorong Zhou, 1 Jianhong Liu, 1 Aifeng Meng, 1 Lihong Zhang, 1 Min Wang, 1 Hong Fan, 2 Wei Peng,corresponding author 1 and Jianwei Lucorresponding author 1
Lung cancer had been leading mounts of deaths worldwide. Advances in genes microarray had helped human further understand genes and identify novel circular RNAs. This study aimed at investigating the biological functions and molecular mechanisms of hsa_circ_0046264 in lung cancer which may be helpful in lung cancer early diagnosis and clinical treatment.
Gene microarray data screened the differential gene of hsa_circ_0046264 and its downstream genes were found by bioinformatics analysis and verified by luciferase reporter assay. QRT-PCR and Western blot was used to detect the RNA and protein levels respectively. RNase R digestion confirmed the existences of circular RNA. Cell viability, invasion and apoptosis were determined by MTT assay, flow cytometry and DNA damage assay. Tumor formation in nude mice and immunohistochemistry proved the functions of hsa_circ_0046264 in vivo.
Hsa_circ_0046264 and BRCA2 were down-regulated in lung cancer tissues while miR-1245 was up-regulated. Hsa_circ_0046264 induced apoptosis but inhibited proliferation and invasion of lung cancer cells through targeting miR-1245 to up-regulate BRCA2. Hsa_circ_0046264 inhibited the tumor growth in vivo.
Hsa_circ_0046264 was a tumor suppressor in lung cancer. Overexpression of hsa_circ_0046264 could up-regulate BRCA2 expression through down-regulating of miR-1245.
Electronic supplementary material
The online version of this article (10.1186/s12931-018-0819-7) contains supplementary material, which is available to authorized users.
hsa_circ_0046264, Hsa-miR-1245, BRCA2, Lung cancer
Hsa_circ_0046264 up-regulated BRCA2 to suppress lung cancer through targeting hsa-miR-1245
Liu Yang,1 Jun Wang,2 Yaodong Fan,3 Kun Yu,4 Baowei Jiao,5 and Xiaosan Sucorresponding author1