[Retracted] Silencing the long noncoding RNA, TINCR, a molecular sponge of miR­335, inhibits the malignant phenotype of epithelial ovarian cancer via FGF2 suppression.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that various panels showing the data from flow cytometry experiments in Figs. 2C, 4C and 6C, and certain of the tumor images featured in Fig. 9A, were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to International Journal of Oncology, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 55: 1110­1124, 2019; DOI: 10.3892/ijo.2019.4875].

Identification of Potential Driver Genes Based on Multi-Genomic Data in Cervical Cancer.

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.

LINC01305 inhibits malignant progression of cervical cancer via miR-129-5p/Sox4 axis.

BACKGROUND: The association between LINC01305, a newly discovered long non-coding RNA (lncRNA), and cervical cancer (CC) has been poorly analyzed. In the present study, we revealed high expression of LINC01305 in CC by the cancer genome atlas (TCGA) and Gene Expression Omnibus (GEO), and dissected the related mechanisms. METHODS: LINC01305, microRNA (miR) -129-5p and SRY-related high-mobility group box 4 (Sox4) mRNA levels were quantitated by quantitative reverse transcription-PCRy qRT-PCR). CC tissues and cell lines and corresponding controls were enrolled for the quantification of LINC01305 expression in CC. Effects of LINC01305 and miR-129-5p on cell proliferation, metastasis, and apoptosis were evaluated by MTT, colony formation, wound healing, Transwell and flow cytometry assays. Sox4 protein levels were tested by Western blot (WB). Bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down and dual-luciferase reporter (DLR) assay were performed to determine molecular mechanisms of LINC01305 in CC. Xenograft models of CC were constructed to evaluate the role of LINC01305 in vivo. RESULTS: The expression of LINC01305 was evidently elevated in CC tissues and cell lines than that in controls and associated with clinicopathological features. Downregulating LINC01305 suppressed malignant phenotypes (proliferation, migration, invasion) of Hela and SiHa cells. In addition, silencing miR-129-5p by its inhibitor eliminated the inhibition of growth and metastasis induced by LINC01305 siRNA. Sox4 might serve as a direct target for miR-129-5p and was negatively regulated by miR-129-5p and LINC01305. CONCLUSION: LINC01305 acts as a competitive endogenous RNA (ceRNA) and regulates Sox4 via sponging miR-129-5p, contributing to the diagnosis and treatment of CC.

Silencing the long noncoding RNA, TINCR, a molecular sponge of miR­335, inhibits the malignant phenotype of epithelial ovarian cancer via FGF2 suppression.

Aberrant terminal differentiation­induced 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 transcription­quantitative polymerase chain reaction. Cell Counting Kit­8 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 tumor­promoting 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 microRNA­335 (miR­335) in EOC cells, thereby regulating fibroblast growth factor 2 (FGF2) expression. miR­335 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 miR­335, 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.

PFN2, a novel marker of unfavorable prognosis, is a potential therapeutic target involved in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal 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. METHODS: PFN2 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. RESULTS: Compared 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. CONCLUSIONS: Our 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.