MicroRNA-1976 functions as a tumor suppressor and serves as a prognostic indicator in non-small cell lung cancer by directly targeting PLCE1

Chen, Gang; Hu, Jing; Huang, Zhao; Yang, Lijing; Chen, Min

doi:10.1016/j.bbrc.2016.04.030

Cited by 30 publications

(22 citation statements)

References 24 publications

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“…When addressing the “exclusive lung interactions” the genes CDT1, CENPN, DAPK2, HJURP, KIF20A, NACPD2, NCAPG, NCAPH, SMC1B , and SPC24 have so far not been associated to survival in lung cancer, although most of its associated miRNAs have been. For instance miR-miR-1976 and miR-let-7b-5p miRNAs had already been associated to prognosis in lung cancer4969, and in other tumours like breast70, prostate71, and gastric72. In conclusion, our analysis has revealed novel miRNA-gene correlations that associate with patient prognosis, supported by previous findings on different tumour types.…”

Section: Discussionsupporting

confidence: 87%

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Novel miRNA-mRNA interactions conserved in essential cancer pathways

Andrés-León

Cases²,

Alonso

et al. 2017

Sci Rep

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Cancer is a complex disease in which unrestrained cell proliferation results in tumour development. Extensive research into the molecular mechanisms underlying tumorigenesis has led to the characterization of oncogenes and tumour suppressors that are key elements in cancer growth and progression, as well as that of other important elements like microRNAs. These genes and miRNAs appear to be constitutively deregulated in cancer. To identify signatures of miRNA-mRNA interactions potentially conserved in essential cancer pathways, we have conducted an integrative analysis of transcriptomic data, also taking into account methylation and copy number alterations. We analysed 18,605 raw transcriptome samples from The Cancer Genome Atlas covering 15 of the most common types of human tumours. From this global transcriptome study, we recovered known cancer-associated miRNA-targets and importantly, we identified new potential targets from miRNA families, also analysing the phenotypic outcomes of these genes/mRNAs in terms of survival. Further analyses could lead to novel approaches in cancer therapy.

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Section: Discussionsupporting

confidence: 87%

“…Moreover, they are involved in the majority of these lung exclusive interactions, suggesting a potential value of these miRNAs as biomarkers for lung cancer. In fact miR-1976 is a potential tumour suppressor in lung cancer, as described in relation with the oncogene PLCE1 49.…”

Section: Discussionmentioning

confidence: 99%

Novel miRNA-mRNA interactions conserved in essential cancer pathways

Andrés-León

Cases²,

Alonso

et al. 2017

Sci Rep

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“…Yu et al reported that PLCE1 -positive expression was significantly related to the lower 5-year survival rate in gastric cancer 23. Moreover, Chen et al reported that the low expression of miR-1976 (which can regulate mRNA expression directly by targeting the 3′-untranslated region [UTR] of PLCE1 ) is correlated with poor clinical prognosis in NSCLC parents 19. In our study, we demonstrated that HCC parents with negative PLCE1 expression had a markedly shorter OS and RFS than those with positive PLCE1 expression by log-rank test.…”

Section: Discussionsupporting

confidence: 50%

“…Therefore, recent studies had demonstrated that the abnormal expression of PLCE1 in human tissues may be related to initiation and development of cancer. For example, through their semi-quantitative analysis study, Chen et al had indicated that the overexpression of PLCE1 was significantly correlated with esophageal squamous cell carcinoma and non-small cell lung cancer (NSCLC),13,19 whereas in the study of Wang et al, PLCE1 can serve as a cancer suppressor gene in colon cancer, which inhibited the proliferation of tumor cells 20. Furthermore, Li et al found that knockdown of PLCE1 can markedly increase the expression of p53 in esophageal cancer cells, indicating that overexpression of PLCE1 may promote the formation and development of tumor cells 21.…”

Section: Discussionmentioning

confidence: 99%

Low <em>PLCE1</em> levels are correlated with poor prognosis in hepatocellular carcinoma

Cheng

Xing

Jia

et al. 2016

OTT

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BackgroundPrevious reports show that phospholipase C epsilon-1 (PLCE1) expression is positively correlated with esophageal squamous cell carcinoma and gastric cardia adenocarcinomas; however, the expression of PLCE1 in hepatocellular carcinoma (HCC) and its correlation with clinical outcome still remain unclear. The aim of this study was to explore the expression of PLCE1 in HCC tissue and to determine whether PLCE1 was a prognostic factor for HCC patients.Materials and methodsPLCE1 levels in 20 paired HCC tissues and corresponding paracarcinomatous tissues was investigated by quantitative real-time polymerase chain reaction and Western blot assays. In addition, protein levels of PLCE1 in one normal liver epithelial cell and four HCC cell lines were examined using Western blot assay. Moreover, immunohistochemistry was applied to determine the expression of PLCE1 in HCC and corresponding surrounding tissues from 90 patients. Statistical analyses were used to examine the association between PLCE1 levels and clinicopathological features.ResultsWe found that the expression of PLCE1 in tumor tissues was significantly lower than those in paracarcinomatous tissues at both mRNA and protein levels (P<0.05). We also determined that PLCE1 protein expression levels were lower in HCC cell lines than normal liver epithelial cells (P<0.05). Notably, immunohistochemical assay showed that PLCE1 expression was significantly low in HCC tissues compared with the adjacent normal liver tissues (40% vs 18.9%; P<0.05). Besides, PLCE1 levels were negatively correlated with tumor capsulae, vascular invasion, Edmondson grade, alpha-fetoprotein, and tumor-node-metastasis stage (P<0.05). Univariate analysis revealed that lower level expression of PLCE1 was significantly associated with poorer overall survival (OS) rate (P<0.001) and disease-free survival rate (P<0.001). Multivariate analysis revealed that low PLCE1 level was an independent poor prognostic factor of OS and recurrence-free survival (P<0.001 and P=0.003, respectively).ConclusionIn brief, our results revealed that decreased PLCE1 expression was associated with tumor progression in HCC and may function as a promising biomarker for HCC prognosis.

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“…It has been suggested to play a tumor suppressor role in and decrease the incidence of colorectal carcinoma (CRC) [39–41]. However, PLCE1 is thought to act as an oncogene in bladder cancer [42, 43], non-small cell lung cancer [44], skin cancer [45], and head and neck cancer [46]. Upregulation of PLCE1 mRNA level is associated with longer survival in gastric cardia adenocarcinoma (GCA) and ESCC, while the transcript is downregulated in GCA and ESCC tumor tissue [47], which was confirmed by another study of ESCC patients [30].…”

Section: Discussionmentioning

confidence: 99%

PLCE1 polymorphisms and expression combined with serum AFP level predicts survival of HBV-related hepatocellular carcinoma patients after hepatectomy

et al. 2017

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Polymorphisms in the phospholipase C epsilon (PLCE) 1 gene play a crucial role in the development and progression of several types of cancer. The present study investigated the prognostic significance of PLCE1 gene polymorphisms and expression combined with serum α-fetoprotein (AFP) level in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Single nucleotide polymorphisms were genotyped by sequencing DNA isolated from surgically resected tumor samples of 421 HBV-related HCC patients, and expression profiles were generated based on the GSE14520 dataset. A joint-effects analysis of PLCE1 haplotypes (Ars2274223Crs3765524; Grs2274223Trs3765524) with AFP level stratified at 20 ng/ml showed a significant association with overall survival(OS) of HBV-related HCC patients(log-rank P=0.0003). Patients with AC and GT haplotypes with AFP level ≥ 20 ng/ml had an increased risk of death as compared to those with the AC haplotype and AFP level < 20 ng/ml (adjusted P=0.029 and 0.041, respectively). Patients with the GT haplotype and AFP level < 20 ng/ml also had an increased risk of death, although with a non-significant P value (adjusted P=0.092). Joint-effects analysis of PLCE1 mRNA expression with serum AFP level stratified at 300 ng/ml was significantly associated with HBV-related HCC recurrence and OS. Our results demonstrate that PLCE1 haplotypes (including rs2274223 and rs3765524) and expression combined with serum AFP level may predict postoperative outcome of HBV-related HCC patients.

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MicroRNA-1976 functions as a tumor suppressor and serves as a prognostic indicator in non-small cell lung cancer by directly targeting PLCE1

Cited by 30 publications

References 24 publications

Novel miRNA-mRNA interactions conserved in essential cancer pathways

Novel miRNA-mRNA interactions conserved in essential cancer pathways

Low <em>PLCE1</em> levels are correlated with poor prognosis in hepatocellular carcinoma

PLCE1 polymorphisms and expression combined with serum AFP level predicts survival of HBV-related hepatocellular carcinoma patients after hepatectomy

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