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Previous studies have reported that triple-negative breast cancer is more sensitive to cytotoxic treatment, compared with estrogen receptor (ER)-positive cancer. However, the underlying molecular mechanisms remain to be fully elucidated. In the present study, we employed reverse transcription-quantitative polymerase chain reaction, western blot and in vivo assays to investigate the underlying mechanisms. The sensitivities of cells to cisplatin were examined in ER-positive and ER-negative breast cancer cells, and it was found that the ER-negative cells were more sensitive to cisplatin, compared with the ER-positive cells. In addition, it was found that mitochondrial transcription factor A (TFAM), which functions in mitochondrial DNA replication and repair, was expressed at a high level in ER-positive cell lines and patient tissues, compared with ER-negative cell lines and tissues. It was also found that the sensitivity to cisplatin was decreased when TFAM was knocked down in the breast cancer cells, and these effects were reversed when TFAM was reintroduced to the cells. Similar results were observed in xenograft tumors. The results of the present study provided evidence that resistance to cisplatin chemotherapy in ER-positive breast cancer may be through TFAM and indicated that TFAM may be a target for chemoresistance in patients with breast cancer. These findings offer potential guidance for chemotherapy in patients with breast cancer. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the variations of the gene network and biological functions induced by hsa‑miR‑145‑5p in the laryngeal squamous cell carcinoma (LSCC) cell line Tu‑177. A hsa‑miR‑145‑5p‑overexpressed Tu‑177 cell model was established, and the gene expression microarray data of miR‑145‑5p‑overexpressed cells and negative control (NC) cells were analyzed. The differentially expressed genes (DEGs) between two groups were identified, and their potential functions were predicted by functional enrichment analysis. Furthermore, the targets of miR‑145‑5p were identified from the DEGs, and their potential functions and protein‑protein interactions (PPIs) were analyzed. The mRNA expressions of acetyl‑CoA carboxylase β (ACACB), fibroblast growth factor receptor 1 (FGFR1), protein phosphatase 3 catalytic subunit a (PPP3CA) and spleen associated tyrosine kinase (SYK), were analyzed via quantitative polymerase chain reaction. A total of 1,501 upregulated and 887 downregulated genes were identified in the hsa‑miR‑145‑5p‑overexpressed Tu‑177 cells, compared with the NC cells. Of these DEGs, 164 upregulated and 221 downregulated genes were predicted to be targeted by hsa‑miR‑145‑5p. The upregulated target genes were primarily associated with functions of immunity, whereas the downregulated target genes were significantly enriched in the p53 signaling pathway. In the PPI network consisting of 267 target genes, the upregulated ACACB had the greatest degree and interacted with downregulated genes including PPP3CA and SYK, in addition to upregulated genes, including FGFR1. The mRNA expressions of ACACB and FGFR1were markedly enhanced in miR‑145‑5p‑overexpressed Tu‑177 cells, whereas overexpressing miR‑145‑5p significantly reduced mRNA expression of PPP3CA and SYK. hsa‑miR‑145‑5p may exhibit an anticancer role in LSCC via regulating multiple cell processes, including cell proliferation and invasion, fatty acid metabolism, immunity and p53 signaling pathway. These findings provide novel information for the future investigation of miR‑145‑5p functions in LSCC. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) have emerged recently as important factors in regulating fundamental biological processes. Alterations in the expression and function of lncRNAs have been observed to promote tumor formation, progression and metastasis. Although downregulation of the expression levels of LET lncRNA in several tumors has been reported, its role in gastric cancer remains unknown. The aim of the present study was to investigate the expression and function of LET in gastric cancer development. The expression levels of LET in 37 pairs of gastric cancer and adjacent non-tumor tissues were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, LET expression in gastric cancer cell lines was analyzed by RT-qPCR assay analysis. Furthermore, the impact of LET on cell proliferation, migration and apoptosis were detected using the cell counting kit-8, wound scratch and ELISA assays, respectively. The results demonstrated that the expression level of LET was downregulated in gastric cancer tissues and cell lines (SGC-7901 and MGC-803) compared with normal tissues and a normal human gastric epithelial cell line (GES-1). Restoration of LET expression using a synthesized recombinant overexpression vector transfected into SGC-7901 and MGC-803 cells, significantly inhibited cell proliferation and migration, and promoted cell apoptosis in vitro. The present study is the first to demonstrate that LET may function as a tumor suppressor in gastric cancer. The results indicate that LET may be a promising biomarker and/or a therapeutic target for gastric cancer. [ABSTRACT FROM AUTHOR]

Previous experimental studies have demonstrated that hepatocyte growth factor (HGF) and its receptor c-Met serve an important function in lymphangiogenesis, but their biological functions in malignant tumors have remained elusive. The present study aimed to investigate the expression patterns of HGF-α and c-Met and their association with vascular endothelial growth factor (VEGF)-C, lymphatic vessel density and lymph node metastasis in non-small-cell lung cancer (NSCLC). In the present study, the lymphatic microvessel density (LMVD) and the expression levels of HGF-α, its receptor c-Met and VEGF-C were determined in 113 human NSCLC tissues and 113 normal lung tissue samples, using immunohistochemical staining. As a result, it was determined that the expression levels of HGF-α, c-Met and VEGF-C were significantly higher in NSCLC tissues than those in normal lung tissues (HGF-α, 67.3 vs. 20.4%, P<0.001; c-Met, 74.3 vs. 23.0%, P<0.001; and VEGF-C, 65.5 vs. 23.9%, P<0.001). HGF-α expression was observed to be significantly associated with that of VEGF-C (r=0.234, P=0.012) or c-Met (r=0.648, P<0.001). In addition, there was a positive correlation between the expression levels of VEGF-C and c-Met (r=0.224, P=0.017). In NSCLC tissues, the expression of HGF-α, c-Met or VEGF-C was significantly correlated with the LMVD (P=0.045, 0.002 and 0.001, respectively), and lymph node metastasis was more common in HGF-α, c-Met or VEGF-C-positive groups (P=0.020, 0.020 and 0.009, respectively). In addition, the HGF-α or VEGF-C-positive groups presented shorter survival time periods. In conclusion, the expression of HGF-α or c-Met was closely correlated with VEGF-C, LMVD and metastases of lymph nodes, indicating that HGF-α, c-Met and VEGF-C may perform important and collaborative actions in lymphangiogenesis and lymphatic metastasis of primary NSCLC. [ABSTRACT FROM AUTHOR]

Paeonol (Pae) is an herbal extract that has attracted extensive attention for its anti‑cancer effects demonstrated by a number of studies, which have predominantly demonstrated inhibition of cell proliferation and induction of apoptosis. The influence of Pae on cancer cell metastasis has been less widely reported. The present study aimed to investigate the under‑reported effects of Pae on the growth, invasion and migration of poorly differentiated BGC823 gastric cancer cells with strong invasive and metastatic abilities. The anti‑proliferative and pro‑apoptotic effects of Pae on BGC823 cells were verified by Cell Counting kit‑8 and Annexin V‑fluorescein isothiocyanate/ propidium iodide assays. Cell scratch‑wound healing and Transwell methods were applied, and it was demonstrated that Pae could exert inhibitory activities on the invasion and migration of BGC823 cells. Furthermore, it was indicated by western blot analysis that Pae could downregulate the protein expression levels of matrix metalloproteinase (MMP)‑2 and ‑9 in a concentration‑dependent manner, which may support a novel potential mechanism accounting for its anti‑cancer effects on gastric cancer. [ABSTRACT FROM AUTHOR]

Adipose‑derived mesenchymal stromal cells (ADSCs) possess a multilineage potential and immunoregulatory properties, and may have great potential in autologous cell‑based technologies. The aim of the present study was to investigate how the age of patients with benign end‑stage liver disease affected the biological and functional characteristics of ADSCs, which is important for increasing the potential effectiveness of autologous cell therapy. ADSCs were obtained and cultured from three distinct age groups: Infant, adult and elderly. Cell immunophenotypic characteristics and antiapoptotic capacity were determined by flow cytometry, and cell proliferation and migration were monitored with a Real‑Time Cell Analyzer. Multilineage differentiation potential was investigated by evaluating the induction response and by reverse transcription‑quantitative polymerase chain reaction. Suppression of T cell proliferation was assessed in a co‑culture system by MTT assay. The regulatory T cells (Tregs) were analyzed by flow cytometry, and ELISAs were performed to detect the cytokine profile in culture supernatants. All ADSC sample phenotypes were characterized as CD90+/CD73+/CD105+/CD45-/CD34-, and the apoptotic rate was not statistically different among all ages. However, the proliferation and migratory capacity were significantly increased in infant‑derived ADSCs. In addition, ADSCs derived from infant patients demonstrated a relatively high proclivity for osteogenic differentiation compared with cells derived from either adult or elderly patients. Furthermore, ADSCs co‑cultured with mitogen‑activated T cells significantly suppressed T‑cell proliferation, downregulated the secretion of interferon‑γ and increased the percentage of Tregs, with infant‑derived ADSCs being most effective. Results from the present study indicated that ADSCs derived from infant patients may have biological advantages compared with older cell sources, and may provide an effective reference for the clinical application of ADSCs. [ABSTRACT FROM AUTHOR]

Podoplanin and fibroblast growth factor (FGF) 1 have been detected more frequently in lung squamous cell carcinoma (SQCC) compared with lung adenocarcinoma. Furthermore, it has been previous demonstrated that FGF1 is located on the edge of tumor nests in certain lung SQCC sections, which resembles the characteristic expression pattern of podoplanin. Podoplanin and FGF1 have roles in lymphangiogenesis and angiogenesis. Based on their consistently specific expression in lung SQCC and similar localization patterns, the present study aimed to investigate whether the expression of podoplanin in tumor cells is correlated with FGF1 expression in lung SQCC and whether their co-expression has clinicopathological significance, particularly for lymphangiogenesis/angiogenesis. The correlation between podoplanin and FGF1 expression in tumor cells of 82 lung SQCC cases was investigated by immunohistochemical staining and the association between the co-expression of podoplanin and FGF1, and clinicopathological factors such as microvessel density (MVD), was examined in these samples. In addition, the prognostic value of co-expression of podoplanin and FGF1 in tumor cells was determined, and the regulation of FGF1 expression and angiogenesis by podoplanin was examined in vitro in a human lung SQCC cell line. Immunohistochemical analysis demonstrated that there was a significant correlation between podoplanin and FGF1 expression in lung SQCC tumor cells (R=0.591; P<0.0001). Co-expression of podoplanin and FGF1 was significantly associated with larger primary tumor size, advanced TNM stage and higher intratumoral MVD. Survival analysis demonstrated that cases with podoplanin and FGF1 double-positive staining had a significantly lower survival rate compared with cases with double-negative staining. In vitro experiments revealed that podoplanin regulated FGF1 expression and affected tube formation of human umbilical vein endothelial cells. Combined, the results demonstrated that podoplanin was co-expressed with FGF1 in lung SQCC and this co-expression was correlated with poor prognosis. [ABSTRACT FROM AUTHOR]

Rhomboid domain containing 1 (RHBDD1), is a member of the rhomboid protease family, which has a pivotal role in the progression of numerous severe malignancies. However, its role in colorectal carcinoma (CRC) remains to be elucidated. In the present study, RHBDD1 was shown to be widely expressed in CRC cell lines. Lentivirus-mediated RNA interference was employed to knockdown RHBDD1 expression in RKO CRC cells. Functional analyses indicated that depletion of RHBDD1 expression resulted in significantly reduced CRC cell proliferation and colony formation, and induced a G0/G1 phase cell cycle arrest. The findings of the present study suggest that RHBDD1 may contribute to CRC tumorigenesis and serve as a potential therapeutic target in human CRC. [ABSTRACT FROM AUTHOR]