Tumor-associated macrophages (TAMs) in the tumor microenvironment have been associated with enhanced tumor progression. In this study, we investigated the role and molecular mechanisms of MALAT1 in TAMs derived from thyroid cancer. The expression of MALAT1 and FGF2 in thyroid cancer tissues and cells were measured by quantitative real-time PCR and Western blot. TAMs were transfected with indicated constructs. Then the culture medium (CM) from TAMs was harvested for assay. Secreted FGF2 protein levels and TNF-α, IL-12, and IL-10 levels were detected by ELISA. The cell proliferation, migration, and invasion of FTC133 cells were determined with a CCK-8 assay and a Transwell assay, respectively. In addition, HUVEC vasculature formation was measured by matrigel angiogenesis assay. The higher levels of MALAT-1 and FGF2 were observed in thyroid cancer tissues and in thyroid cancer cells compared to that in the control. Besides, in the presence of si-MALAT1, the levels of TNF-α and IL-12 were significantly up-regulated whereas IL-10 was down-regulated in the CM from TAMs. Moreover, down-regulation of MALAT1 in TAMs reduced proliferation, migration, and invasion of FTC133 cells and inhibited angiogenesis. However, overexpression of FGF2 blocked the effects of MALAT1 siRNAs on cell migration, invasion, and angiogenesis. Our results suggest that MALAT1-mediated FGF2 protein secretion from TAMs inhibits inflammatory cytokines release, promotes proliferation, migration, and invasion of FTC133 cells and induces vasculature formation. J. Cell. Biochem. 118: 4821-4830, 2017. © 2017 Wiley Periodicals, Inc.

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In the light of increasing evidence supporting cancer stem cells (CSCs) theory, the expression of two stem cell markers, CD133 and adenosine triphosphate-binding cassette superfamily G member 2 (ABCG2), in esophageal squamous cell carcinoma (ESCC) was investigated, and their prognostic values were evaluated. Paraffin-embedded tissue sections of 110 ESCC patients were investigated using Immunohistochemistry. The association of CD133 and ABCG2 expression with clinicopathologic characteristics was analyzed by χ(2) test. Survival analysis was carried out using Kaplan-Meier method and Cox proportional hazards model. CD133 and ABCG2 expression were detected in 27.3% and 15.5% of ESCC patients, respectively. The presence of CD133-positive cancer cells was associated with tumor cell differentiation (P= 0.008) but not significantly related to the survival of ESCC patients (P= 0.085). ABCG2 expression was not associated with clinicopathologic characteristics but was a significant prognostic factor for adverse overall survival of ESCC patients (P= 0.005). The median overall survival time for ESCC patients with and without ABCG2 expression were 21.8 and >49.3 months, respectively. A combined analysis of CD133 and ABCG2 expression did not show that ESCC patients with coexpression of these two markers had a worse prognosis than those with only ABCG2 expression (P= 0.934). Moreover, ABCG2 expression was revealed to be an independent prognostic factor along with tumor node metastasis stage in multivariate analysis (hazard ratio of ABCG2, 3.38; 95% confidence interval, 1.61∼7.09; P= 0.001). By survival analysis based on tumor node metastasis stage of ESCC, the association between ABCG2 expression and the patients' prognosis was found significant in the group of relatively early stage (P= 0.005) and marginally significant in the group of relatively late stage (P= 0.058). This is the first time to report the presence of CD133-positive cancer cells in ESCC but not supporting its prognostic value and validity as a CSC marker for ESCC. ABCG2 expression was found to correlate with the survival of ESCC patients, especially those at relatively early stage, suggesting that ABCG2-positive cancer cells may represent a pool of CSCs in ESCC, and relatively early-stage patients with ABCG2 expression may deserve more intensive or targeted therapy.

Triple negative breast cancer lacking estrogen receptor (ER), progesterone receptor and Her2 account for account for the majority of the breast cancer deaths, due to the lack of specific gene targeted therapy. Our current study aimed to investigate the role of miR-544 in triple negative breast cancer. Endogenous levels of miR-544 were significantly lower in breast cancer cell lines than in human breast non-tumorigenic and mammary epithelial cell lines. We found that miR-544 directly targeted the 3'-untranslated region (UTR) on both Bcl6 and Stat3 mRNAs, and overexpression of miR-544 in triple negative breast cancer cells significantly down-regulated expressions of Bcl6 and Stat3, which in turn severely inhibited cancer cell proliferation, migration and invasion in vitro. Employing a mouse xenograft model to examine the in vivo function of miR-544, we found that expression of miR-544 significantly repressed the growth of xenograft tumors. Our current study reported miR-544 as a tumor-suppressor microRNA particularly in triple negative breast cancer. Our data supported the role of miR-544 as a potential biomarker in developing gene targeted therapies in the clinical treatment of triple negative breast cancer.