MiR-449a suppresses the epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma by multiple targets

Chen, Shupeng; Liu, Baoxin; Xu, Jie; Pei, Xin; Liao, Yiji; Yuan, Feng; Zheng, Fang

doi:10.1186/s12885-015-1738-3

Cited by 61 publications

(62 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, miR‐449a expression was increased in luminal BC compared to the other subtypes (Dvinge et al., 2013) and its tumor suppressor activity was regulated by PI3K (Liu et al., 2015). The upregulated expression of miR‐205 and miR‐449a in tumors with a PIK3CA mutation was shown to suppress the epithelial mesenchymal transition (EMT) in BC and liver cancer, respectively (De Cola et al., 2015) (Chen et al., 2015a). Interestingly, miR‐205‐5p directly targets HER3 receptor, involved as well in EMT, inhibiting the PI3K pathway activation respectively (De Cola et al., 2015).…”

Section: Discussionmentioning

confidence: 99%

LRG1 mRNA expression in breast cancer associates with PIK3CA genotype and with aromatase inhibitor therapy outcome

et al. 2016

View full text Add to dashboard Cite

Background PIK3CA is the most frequent somatic mutated oncogene in estrogen receptor (ER) positive breast cancer. We previously observed an association between PIK3CA genotype and aromatase inhibitors (AI) treatment outcome. This study now evaluates whether expression of mRNAs and miRs are linked to PIK3CA genotype and are independently related to AI therapy response in order to define potential expressed biomarkers for treatment outcome. Materials and methods The miR and mRNA expression levels were evaluated for their relationship with the PIK3CA genotype in two breast tumor datasets, i.e. 286 luminal cancers from the TCGA consortium and our set of 84 ER positive primary tumors of metastatic breast cancer patients who received first line AI. BRB Array tools class comparison was performed to define miRs and mRNAs whose expression associate with PIK3CA exon 9 and 20 status. Spearman correlations established miR–mRNA pairs and mRNAs with related expression. Next, a third dataset of 25 breast cancer patients receiving neo‐adjuvant letrozole was evaluated, to compare expression levels of identified miRs and mRNAs in biopsies before and after treatment. Finally, to identify potential biomarkers miR and mRNA levels were related with overall survival (OS) and progression free survival (PFS) after first‐line AI therapy. Results Expression of 3 miRs (miR‐449a, miR‐205‐5p, miR‐301a‐3p) and 9 mRNAs (CCNO, FAM81B, LRG1, NEK10, PLCL1, PGR, SERPINA3, SORBS2, VTCN1) was related to the PIK3CA status in both datasets. All except miR‐301a‐3p had an increased expression in tumors with PIK3CA mutations. Validation in a publicly available dataset showed that LRG1, PGR, and SERPINA3 levels were decreased after neo‐adjuvant AI‐treatment. Six miR–mRNA pairs correlated significantly and stepdown analysis of all 12 factors revealed 3 mRNAs (PLCL1, LRG1, FAM81B) related to PFS. Further analyses showed LRG1 and PLCL1 expression to be unrelated with luminal subtype and to associate with OS and with PFS, the latter independent from traditional predictive factors. Conclusion We showed in two datasets of ER positive and luminal breast tumors that the expression of 3 miRs and 9 mRNAs associate with the PIK3CA status. Expression of LRG1 is independent of luminal (A or B) subtype, decreased after neo‐adjuvant AI‐treatment, and is proposed as potential biomarker for AI therapy outcome.

show abstract

Section: Discussionmentioning

confidence: 99%

LRG1 mRNA expression in breast cancer associates with PIK3CA genotype and with aromatase inhibitor therapy outcome

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Several miRNAs involved in negative regulation of the TGFbmediated epithelial-to-mesenchymal transition (EMT), including miR-200 family members (miR-200 b, miR-200 c, miR-429), miR-93 and miR-449 a [62,73,76], were found to be upregulated in DCIS (Table 1) which are both activators of TGFb-mediated EMT [66,67], were upregulated in DCIS (Table 1). Moreover, as shown in Table 1, non-histone chromatin-binding protein HMGA2, a mediator of TGFb signaling, is a target of let-7 [77].…”

Section: Mirnas Upregulated In Dcismentioning

confidence: 99%

Noncoding RNAs in breast cancer

Lo¹,

Wolfson²,

Zhou³

et al. 2015

Briefings in Functional Genomics

View full text Add to dashboard Cite

The mammalian transcriptome has recently been revealed to encompass a large number of noncoding RNAs (ncRNAs) that play a variety of important regulatory roles in gene expression and other biological processes. MicroRNAs (miRNAs), the best studied of the short noncoding RNAs (sncRNAs), have been extensively characterized with regard to their biogenesis, function and importance in tumorigenesis. Another class of sncRNAs called piwi-interacting RNAs (piRNAs) has also gained attention recently in cancer research owing to their critical role in stem cell regulation. Long noncoding RNAs (lncRNAs) of >200 nucleotides in length have recently emerged as key regulators of developmental processes, including mammary gland development. lncRNA dysregulation has also been implicated in the development of various cancers, including breast cancer. In this review, we describe and discuss the roles of sncRNAs (including miRNAs and piRNAs) and lncRNAs in the initiation and progression of breast tumorigenesis, with a focus on outlining the molecular mechanisms of oncogenic and tumor-suppressor ncRNAs. Moreover, the current and potential future applications of ncRNAs to clinical breast cancer research are also discussed, with an emphasis on ncRNA-based diagnosis, prognosis and future therapeutics.

show abstract

“…Clinically, miR‐23b expression has been associated with improved PFS or OS in patients with ovarian, prostate, and renal cancer but with worse outcomes in patients with breast cancer . miR‐449a and miR‐449b, which have overlapping targets, directly interact with cell‐cycle regulators and oncogenes like cyclin‐dependent kinase 6 (CDK6), cell division cycle 25A (CDC25A), histone deacetylase 1 (HDAC1), hepatocyte growth factor receptor (MET), and Finkel‐Biskis‐Jinkins murine osteogenic sarcoma viral oncogene homolog (FOS) . miR‐449b expression increases the risk of recurrence in patients with prostate cancer .…”

Section: Discussionmentioning

confidence: 99%

“…[31][32][33][34][35] miR-449a and miR-449b, which have overlapping targets, directly interact with cell-cycle regulators and oncogenes like cyclin-dependent kinase 6 (CDK6), cell division cycle 25A (CDC25A), histone deacetylase 1 (HDAC1), hepatocyte growth factor receptor (MET), and Finkel-Biskis-Jinkins murine osteogenic sarcoma viral oncogene homolog (FOS). [35][36][37][38] miR-449b expression increases the risk of recurrence in patients with prostate cancer. 39 Paradoxically, tumor-suppressive effects of miR-449a and miR-449b have been reported in vitro.…”

Section: Discussionmentioning

confidence: 99%

Clinical and molecular markers of long‐term survival after oligometastasis‐directed stereotactic body radiotherapy (SBRT)

Wong

Watson

Pitroda

et al. 2016

Cancer

110

View full text Add to dashboard Cite

BACKGROUND:The selection of patients for oligometastasis-directed ablative therapy remains a challenge. The authors report on clinical and molecular predictors of survival from a stereotactic body radiotherapy (SBRT) dose-escalation trial for oligometastases. METHODS: Patients who had from 1 to 5 metastases, a life expectancy of >3 months, and a Karnofsky performance status of >60 received escalating SBRT doses to all known cancer sites. Time to progression, progression-free survival, and overall survival (OS) were calculated at the completion of SBRT, and clinical predictors of OS were modeled. Primary tumor microRNA expression was analyzed to identify molecular predictors of OS. RESULTS: Sixty-one evaluable patients were enrolled from 2004 to 2009. The median follow-up was 2.3 years for all patients (range, 0.2-9.3 years) and 6.8 years for survivors (range, 2.0-9.3 years). The median, 2-year, and 5-year estimated OS were 2.4 years, 57%, and 32%, respectively. The rate of progression after SBRT was associated with an increased risk of death (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.24-1.82). The time from initial cancer diagnosis to metastasis (HR, 0.98; 95% CI, 0.98-0.99), the time from metastasis to SBRT (HR, 0.98; 95% CI, 0.98-0.99), and breast cancer histology (HR, 0.12; 95% CI, 0.07-0.37) were significant predictors of OS. In an exploratory analysis, a candidate classifier using expression levels of 3 microRNAs (miR-23b, miR-449a, and miR-449b) predicted survival among 17 patients who had primary tumor microRNA expression data available. CONCLUSIONS: A subset of oligometastatic patients achieves long-term survival after metastasis-directed SBRT. Clinical features and primary tumor microRNA expression profiling, if validated in an independent dataset, may help select oligometastatic patients most likely to benefit from metastasis-directed therapy. Cancer 2016;122:2242

show abstract

MiR-449a suppresses the epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma by multiple targets

Cited by 61 publications

References 44 publications

LRG1 mRNA expression in breast cancer associates with PIK3CA genotype and with aromatase inhibitor therapy outcome

LRG1 mRNA expression in breast cancer associates with PIK3CA genotype and with aromatase inhibitor therapy outcome

Noncoding RNAs in breast cancer

Clinical and molecular markers of long‐term survival after oligometastasis‐directed stereotactic body radiotherapy (SBRT)

Contact Info

Product

Resources

About