BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most aggressively malignant tumors with dismal prognosis. Profilin 2 (PFN2) is an actin-binding protein that regulates the dynamics of actin polymerization and plays a key role in cell motility. Recently, PFN2 have emerged as significant regulators of cancer processes. However, the clinical significance and biological function of PFN2 in ESCC remain unclear.MethodsPFN2 protein expression was validated by immunohistochemistry (IHC) on tissue microarray from Chinese Han and Kazakh populations with ESCC. The associations among PFN2 expression, clinicopathological features, and prognosis of ESCC were analyzed. The effects on cell proliferation, invasion and migration were examined using MTT and Transwell assays. Markers of epithelial–mesenchymal transition (EMT) were detected by Western blot analysis.ResultsCompared with normal esophageal epithelium (NEE), PFN2 protein expression was markedly increased in low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and ESCC, increased gradually from LGIN to ESCC, and finally reached high grade in HGIN in the Han population. Similarly, PFN2 protein was more overexpressed in ESCC than in NEE in the Kazakh population. The results of Western blot analysis also showed that PFN2 expression was significantly higher in the ESCC tissue than in a matched adjacent non-cancerous tissue. PFN2 expression was positively correlated with invasion depth and lymph node metastasis. High PFN2 expression was significantly correlated with short overall survival (OS) (P = 0.023). Cox regression analysis revealed that PFN2 expression was an independent prognostic factor for poor OS in ESCC. Downregulation of PFN2 inhibited, rather than proliferated, cell invasion and migration, as well as induced an EMT phenotype, including increased expression of epithelial marker E-cadherin, decreased mesenchymal marker Vimentin, Snail, Slug and ZEB1, and morphological changes in ESCC cells in vitro.ConclusionsOur findings demonstrate that PFN2 has a novel role in promoting ESCC progression and metastasis and portending a poor prognosis, indicating that PFN2 could act as an early biomarker of high-risk population. Targeting PFN2 may offer a promising therapeutic strategy for ESCC treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0884-y) contains supplementary material, which is available to authorized users.

Background: Cervical cancer became the third most common cancer among women, and genome characterization of cervical cancer patients has revealed the extensive complexity of molecular alterations. However, identifying driver mutation and depicting molecular classification in cervical cancer remain a challenge.Methods: We performed an integrative multi-platform analysis of a cervical cancer cohort from The Cancer Genome Atlas (TCGA) based on 284 clinical cases and identified the driver genes and possible molecular classification of cervical cancer.Results: Multi-platform integration showed that cervical cancer exhibited a wide range of mutation. The top 10 mutated genes were TTN, PIK3CA, MUC4, KMT2C, MUC16, KMT2D, SYNE1, FLG, DST, and EP300, with a mutation rate from 12 to 33%. Applying GISTIC to detect copy number variation (CNV), the most frequent chromosome arm-level CNVs included losses in 4p, 11p, and 11q and gains in 20q, 3q, and 1q. Then, we performed unsupervised consensus clustering of tumor CNV profiles and methylation profiles and detected four statistically significant expression subtypes. Finally, by combining the multidimensional datasets, we identified 10 potential driver genes, including GPR107, CHRNA5, ZBTB20, Rb1, NCAPH2, SCA1, SLC25A5, RBPMS, DDX3X, and H2BFM.Conclusions: This comprehensive analysis described the genetic characteristic of cervical cancer and identified novel driver genes in cervical cancer. These results provide insight into developing precision treatment in cervical cancer.

Aberrant terminal differentiation-induced noncoding RNA (TINCR) expression has been identified in multiple human cancer types and is functionally significant in cancer progression. However, to the best of our knowledge, no reported studies have investigated the expression pattern and precise role of TINCR in epithelial ovarian cancer (EOC). Here, TINCR expression levels in EOC tissues and cell lines were determined by reverse transcription-quantitative polymerase chain reaction. Cell Counting Kit-8 assays, flow cytometric analysis, Transwell migration and invasion assays, and in vivo xenograft experiments were performed to determine the influence of TINCR on the malignant phenotype of EOC cells in vitro and in vivo. The molecular mechanisms associated with the tumor-promoting roles of TINCR during EOC progression were elucidated using a series of experiments. TINCR expression was higher in EOC tissues and cell lines compared with normal cells. An analysis of the association between TINCR expression and clinicopathological characteristics showed that increased TINCR expression was closely related to tumor size, FIGO stage, and lymphatic metastasis. In addition, the overall survival rates of EOC patients with high TINCR expression levels were lower than in those with low TINCR expression levels. Functional experiments showed that TINCR deficiency attenuated the proliferation, migration, and invasion of EOC cells in vitro and hindered EOC tumor growth in vivo. In addition, EOC cell apoptosis increased after TINCR knockdown. Mechanistically, TINCR was shown to function as a sponge of microRNA-335 (miR-335) in EOC cells, thereby regulating fibroblast growth factor 2 (FGF2) expression. miR-335 inhibition partially counteracted the effect of TINCR knockdown on the aggressive behavior of EOC cells. This study showed, for the first time to the best of our knowledge, that silencing TINCR, which interacts with miR-335, inhibited EOC progression in vitro and in vivo by decreasing FGF2 expression. Hence, this lncRNA could be a potential prognostic biomarker and effective target for therapeutic intervention in EOC.