WAP four-disulfide core domain protein 2 promotes metastasis of human ovarian cancer by regulation of metastasis-associated genes.

BACKGROUND: WAP four-disulfide core domain protein 2 (WFDC2) shows a tumor-restricted upregulated pattern of expression in ovarian cancer. METHODS: In this study, we evaluated the role of WFCD2 in tumor mobility, invasion and metastasis of ovarian cancer in clinical tissue and in ovarian cancer cells, both in vitro and in vivo. RESULTS: Our results revealed WFCD2 was overexpressed in ovarian tissues, and the expression level of WFCD2 was associated with metastasis and lymph node metastasis. Higher expression of WFCD2 was also observed in aggressive HO8910-PM cells than in HO8910 cells, and WFCD2 knockdown halted cell migration, invasion, tumorigenicity and metastasis in ovarian cancer cells, both in vitro and in vivo. Knockdown of WFDC2 induced the down-regulation of ICAM-1, CD44, and MMP2. CONCLUSION: In summary, our work demonstrates that WFCD2 promotes metastasis in ovarian cancer. These findings suggest that WFCD2 plays a critical role in promoting metastasis and may constitute a potential therapeutic target of ovarian cancer

WAP four-disulfide core domain protein 2 gene(WFDC2) is a target of estrogen in ovarian cancer cells

BACKGROUND: WAP four-disulfide core domain protein 2 (WFDC2) shows a tumor-restricted upregulated pattern of expression in ovarian cancer. METHODS: We investigated the role of estradiol (E2) on cell growth in estrogen-sensitive or estrogen-insensitive ovarian cancer cell lines. Real-time (RT)-PCR and western blotting were used to examine the expression of WFDC2 at RNA and protein levels. Growth traits of cells transfected with WFDC2-shRNA or blank control were assessed using MMT arrays. Cell apoptosis was analyzed using annexin V-FITC/PI and flow cytometry. Estrogen receptor expression was evaluated using RT-PCR and flow cytometry. Apoptosis-related proteins induced by E2 directly and indirectly were determined using an antibody array comparing cells transfected with WFDC2- shRNA or a blank control. RESULTS: High-dose (625 ng/ml) E2 increased the expression of WFDC2 in HO8910 cells at both the mRNA and protein levels. However, E2 had no effect on WFDC2 expression in estrogen-insensitive SKOV3 cells. Of interest, knockdown of WFDC2 enabled a considerable estrogen response in SKOV3 cells in terms of proliferation, similar to estrogen-responsive HO8910 cells. This transformation of SKOV3 cells into an estrogen-responsive phenotype was accompanied by upregulation of estrogen receptor beta (ERß) and an effect on cell apoptosis under E2 treatment by regulating genes related to cell proliferation and apoptosis. CONCLUSIONS: We postulate that increased WFDC2 expression plays an important role in altering the estrogen pathway in ovarian cancer, and the identification of WFDC2 as a new player in endocrine-related cancer encourages further studies on the significance of this gene in cancer development and therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13048-015-0210-y) contains supplementary material, which is available to authorized users

Correction to: MicroRNA-214-3p inhibits proliferation and cell cycle progression by targeting MELK in hepatocellular carcinoma and correlates cancer prognosis

Abstract After publication of the original article (1) it was noted that the author details and affiliations of this manuscript contained minor errors in the institution addresses

MicroRNA-214-3p inhibits proliferation and cell cycle progression by targeting MELK in hepatocellular carcinoma and correlates cancer prognosis

Abstract Background MicroRNAs are considered as potential regulators in various biological pathways and contribute to the diagnosis and prognosis of cancers. MicroRNA-214-3p (miR-214-3p) was proved to be correlated with various cancers in recent studies. However, the biological functions of miR-214-3p in hepatocellular carcinoma (HCC) and its association with the prognosis of HCC after liver transplantation are still unevaluated. Here we intended to elucidate the functional implication of miR-214-3p in regulation of cell proliferation and apoptosis and its potential prediction of clinical prognosis of HCC patients. Methods Expressions of miR-214-3p in 98 HCC patients and three HCC cell lines were detected by quantitative reverse transcription PCR (qRT-PCR) to explore the association of miR-214-3p expression and clinicopathological characteristics. The effects of miR-214-3p on cell proliferation and apoptosis were examined by proliferation and flow cytometry assay, respectively. The direct target gene of miR-214-3p was also detected by luciferase reporter assay. Results The effects of miR-214-3p on cell proliferation and apoptosis were examined by proliferation and flow cytometry assay, respectively. The direct target gene of miR-214-3p was also detected by luciferase reporter assay. The results showed that miR-214-3p expression was downregulated in primary HCC samples compared with normal liver tissues, and was decreased in HCC recurrence species compared with non-recurrence controls (P = 0.001). Low miR-214-3p level was associated with poor overall survival (OS) (Log rank P = 0.003) and recurrence-free survival (RFS) (Log rank P = 0.007). Moreover, miR-214-3p precursor transfection resulted in decreased cell proliferation, cell cycle arrest at G1 phase, and enhanced cell apoptosis in HepG2 and HUH-7 cells. Further investigation showed that miR-214-3p could regulate its target gene maternal embryonic leucine zipper kinase (MELK) by directly binding to MELK-3′-UTR. Conclusions miR-214-3p suppresses HCC progression by directly down-regulating MELK expression, indicating a potential therapeutic target for the treatment and prognosis of HCC patients

Integrating cfDNA liquid biopsy and organoid-based drug screening reveals PI3K signaling as a promising therapeutic target in colorectal cancer

Abstract Background The current precision medicine relies on biomarkers, which are mainly obtained through next-generation sequencing (NGS). However, this model failed to find effective drugs for most cancer patients. This study tried to combine liquid biopsy with functional drug tests using organoid models to find potential drugs for cancer patients. Methods Colorectal cancer (CRC) patients were prospectively enrolled and blood samples were collected from patients before the start of treatment. Targeted deep sequencing of cfDNA samples was performed using a 14-gene panel. Gastrointestinal (GI) cancer organoids were established and PI3K and mTOR inhibitors were evaluated on organoid models. Results A total of 195 mutations were detected across 58 cfDNA samples. The most frequently mutated genes were KRAS, TP53, PIK3CA, and BRAF, all of which exhibited higher mutation rates than tissue biopsy. Although 81% of variants had an allele frequency of less than 1%, certain mutations in KRAS, TP53, and SMAD4 had high allele frequencies exceeding 10%. Notably, among the seven patients with high allele frequency mutations, six had metastatic tumors, indicating that a high allele frequency of ctDNA could potentially serve as a biomarker of later-stage cancer. A high rate of PIK3CA mutation (31 out of 67, or 46.3%) was discovered in CRC patients, suggesting possible tumor progression mechanisms and targeted therapy opportunities. To evaluate the value of anti PI3K strategy in GI cancer, different lines of GI cancer organoids were established. The organoids recapitulated the morphologies of the original tumors. Organoids were generally insensitive to PI3K inhibitors. However, CRC-3 and GC-4 showed response to mTOR inhibitor Everolimus, and GC-3 was sensitive to PI3Kδ inhibitor Idelalisib. The CRC organoid with a PIK3CA mutation showed greater sensitivity to the PI3K inhibitor Alpelisib than wildtype organoids, suggesting potential treatment options for the corresponding patients. Conclusion Liquid biopsy holds significant promise for improving precision treatment and tumor prognosis in colorectal cancer patients. The combination of biomarker-based drug prediction with organoid-based functional drug sensitivity assay may lead to more effective cancer treatment

Additional file 1: Figure S1. of WAP four-disulfide core domain protein 2 gene(WFDC2) is a target of estrogen in ovarian cancer cells

Expression of WFDC2 in SKOV3 cells silences clonal lines. (A) Western blot analysis of expression of WFDC2 and GAPDH in SKOV3 cells. Normalized WFDC2 protein levels in the shRNA-transfected (SKOV3-309, SKOV3-209), mock-transfected SKOV3-NA and control SKOV3 cells. The relative quantities of WFDC2 protein were determined by densitometry and normalized to GAPDH. *P < 0.05 compared with SKOV3-NA; #P < 0.05 compared with SKOV3. (B) Western blot analysis of expression of WFDC2 and GAPDH in HO8910 cells. Normalized WFDC2 protein levels in shRNA-transfected and mock-transfected NA cells. Relative quantities of WFDC2 protein were determined using densitometry and normalized to GAPDH. *P < 0.05 compared with HO8910-NA; (DOC 293 kb

SNHG5 promotes proliferation and induces apoptosis in melanoma by sponging miR-155

Melanoma is the most common malignancy of skin cancer. Small nucleolar RNA host gene 5 (SNHG5), a long non-coding RNA (lncRNA), has been demonstrated to be upregulated in tumor tissues and cells of melanoma

Additional file 1 of Integrating cfDNA liquid biopsy and organoid-based drug screening reveals PI3K signaling as a promising therapeutic target in colorectal cancer

Additional file 1. Figure S1. eEarly-stage tumors identified in a patient with P-J syndrome.. Colonoscopy diagnosis and HE staining of the tumors from a PJS patient. A and B, colonoscopy images showing the polyps (A) and the bulk tumor (B) detected in the ascending colon and sigmoid colon, respectively. C and D, HE staining of the biopsies from A and B at 40x magnification, respectively. E and F, HE staining of the biopsies from A and B at 100x magnification, respectively. The white circles in the plots indicate polys or tumors found under colonoscopy. The scale bars in the plots stand for 625 μm (C and D) or 200 μm (E and F). Figure S2. RNA sequencing analysis of organoid treated with Alpelisib. A, Volcano plot showing the differentially expressed genes comparing Alpelisib treated and control CRC-1 organoid. Genes upregulated in the treated group are depicted in orange, while those downregulated are shown in blue. B, Heatmap of top differentially expressed genes comparing Alpelisib treated and control CRC-1 organoid. C and D, GO analysis of up-regulated genes and down-regulated genes. E, F and G, Gene enrichment plots showing the PI3K_AKT_MTOR, APOPTOSIS, E2F_TARGETS pathways. Table S1. All mutations detected in the liquid biopsy of patients