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The present study aimed to evaluate the expression of human epidermal growth factor receptor (HER4) isoforms and their ligand neuregulin 1 (NRG1) isoforms in human primary colorectal cancer (CRC). The mRNA expression of HER4 isoforms JM-a, JM-b, CYT1 and CYT2, and their ligand isoforms NRG1 I, II and III in CRC tissues and adjacent normal tissues were quantified by reverse transcription-quantitative polymerase chain reaction analysis. Univariate analysis and logistic regression analysis were performed to analyze the association between HER4 and NRG1 expression and lymph node metastasis in CRC. The expression levels of CYT1 (P=0.002), CYT2 (P=0.002) and NRG1 type III (P<0.001) were significantly higher in the CRC tissues than in the adjacent normal tissues. The expression of CYT2 was correlated with tumor stage (P=0.018), lymph node status (P=0.015) and tumor-node-metastasis (P=0.038) in CRC. The expression of NRG1III was correlated with lymph node metastasis, and the expression of CYT2 was associated with the expression of NRG1III (r=0.691, P<0.01). The logistic regression analysis indicated that expression of CYT2 >50 was a risk factor for lymph node metastasis in CRC. In conclusion the expression levels of CYT1, CYT2 and NRG1III were upregulated in CRC. An expression of CYT-2 >50 was identified as a risk factor for lymph node metastasis in CRC. Therefore, CY-2 and NRG1III may be involved in the progression of CRC. [ABSTRACT FROM AUTHOR]

Lung is one of the most common sites for bladder cancer to metastasize. Although the involvement of the epithelial‑to‑mesenchymal transition (EMT) in bladder cancer progression has been established, the mechanism of EMT induction remains unclear. In order to investigate this, T24‑parental (P) and T24‑lung (L) bladder cancer cells were obtained from primary tumors and lung metastatic sites of an animal model with orthotopic spontaneous metastatic bladder cancer, according to a protocol previously described. Compared with T24‑P cells, mesenchymal‑like T24‑L cells exhibited an increased ability in tumor invasion and metastasis, as well as an increased expression of hypoxia‑inducible factor (HIF)‑1α, zinc finger E‑box‑binding homeobox 1 (ZEB1), vimentin and N‑cadherin and lower level of cytokeratin 18 were observed. Mechanistically, it was identified that HIF‑1α increases ZEB1 expression and subsequently regulates the expression of EMT‑related genes in both HIF‑1α knocking down by siRNA and gain‑in HIF‑1α by hypoxia culture cell models. In addition, the expression of HIF‑1α and ZEB1 in bladder cancer tissues were increased compared with normal bladder epithelial tissues, as well as significantly increased in the high‑grade, invasive and metastatic bladder cancer tissues compared with low‑grade, superficial and non‑metastatic bladder cancer tissues by using immune‑histochemical staining assay. Notably, the protein level of HIF‑1α was positively associated with that of ZEB1 in bladder cancer tissues. Results from the present study indicate that HIF‑1α promotes ZEB1 expression and EMT in the T24‑L human bladder cancer lung metastasis animal model, suggesting that HIF‑1α serves an important function in the metastasis of bladder cancer, and HIF‑1α and ZEB1 may be potential targets for inhibiting bladder metastasis in the future. [ABSTRACT FROM AUTHOR]

HIF-1 promotes ZEB1 expression and EMT in a human bladder cancer lung metastasis animal model (B) Wound-healing assay to demonstrate that T24-L cells exhibited higher migration activity than T24-P cells, and T24-L control cells exhibited higher migration activity compared with HIF-1 knockdown T24-L cells. HIF-1 , hypoxia inducible factor-1 ; siRNA, small interfering RNA; T24-L,T24 lung metastasis cells; T24-P, T24 parental cells; NC, negative control. [Extracted from the article]

The long non-coding RNA (lncRNA) HOTAIR is an oncogene, that has been reported to be aberrantly expressed in multiple types of malignant tumor tissues. However, its expression and association with synovial sarcoma (SS) remains unclear. The present study aimed to elucidate the expression level of HOTAIR in SS tissues and also identify its role. Reverse transcription-quantitative PCR was used to detect the expression level of HOTAIR and microRNA (miR)-126 in 54 tissue samples from patients with SS, in 10 tissue samples from synovium tissues of normal patients, and in SW982 cells. The protein expression level was measured using western blot analysis and cellular immunofluorescence. Cellular proliferation, invasion and migration were assessed using MTT, Transwell and wound healing assays, respectively. HOTAIR was expressed at high levels in SS tissues. In contrast, miR-126 was expressed at low levels in SS tissues, and was negatively correlated with HOTAIR expression. HOTAIR knockdown in SW982 cells inhibited cellular proliferation in vitro, but also significantly increased the ratio of cells in the G1/G0 phase of the cell cycle, and decreased the ratio of cells in the G2/S phase. In addition, HOTAIR knockdown inhibited the invasion and migration of the SW982 cells, as observed in the Transwell and wound healing assays. Furthermore, HOTAIR knockdown increased miR-126 expression level and decreased the expression level of stromal cell-derived factor-1 (SDF-1) at the protein level. On the other hand, while miR-126-mimic decreased the protein expression level of SDF-1, miR-126-inhibitor increased its expression level in SW982 cells. Notably, HOTAIR knockdown or SDF-1 knockout significantly decreased the protein expression levels of CDK1, CDK2, cyclin D1, MMP-9, vimentin and N-cadherin, and significantly increased the protein expression levels of p21, p53 and E-cadherin in SW982 cells. HOTAIR was highly expressed in SS tissues, wherein it could promote the proliferation, invasion and migration of SS cells by increasing the expression of SDF-1 via miR-126 inhibition. [ABSTRACT FROM AUTHOR]