No abstract

BackgroundThis study aims to clarify the underlying mechanism for the tumor suppressive function of lnc TUSC7 in chemotherapy resistance of esophageal squamous cell carcinoma (ESCC).MethodsTUSC7, miR-224 and DESC1 expressions in ESCC tissues and cells were detected by qRT-PCR. Protein level of DESC1, EGFR and p-AKT were observed by Western blot. Overall survival was calculated using the Kaplan-Meier method. Dual-luciferase reporter gene assay and RIP assay were used to comfirm TUSC7 binding to miR-224, and miR-224 binding to DESC1. Cell proliferation, apoptosis, and colony formation was detected by MTT, Flow Cytometry and Colony formation assays.ResultsTUSC7 was downregulated in ESCC tissues and cells, and low TUSC7 indicated worse overall survival. The analysis of bioinformatics softwares showed that TUSC7 specifically bound to miR-224, and we proved miR-224 was upregulated in ESCC and negatively correlated with TUSC7 expression. Overexpression of TUSC7/inhibition of miR-224 suppressed cell proliferation, colony formation and chemotherapy resistance of ESCC cells, and promoted cell apoptosis. In addition, we confirmed that miR-224 specifically bound to DESC1, and negatively correlated with DESC1. TUSC7 suppressed the proliferation and chemotherapy resistance of ESCC cells by increasing DESC1 expression via inhibiting miR-224. We also confirmed DESC1 inhibited chemotherapy resistance of ESCC cells via EGFR/AKT. Finally, in vivo experiments demonstrated that overexpression of TUSC7 decreased tumor growth and chemotherapy resistance.ConclusionThese findings suggested TUSC7 suppressed chemotherapy resistance of ESCC by downregulating miR-224 to modulate DESC1/EGFR/AKT pathway.

No abstract

Epigallocatechin‑3‑gallate (EGCG), a major catechin in green tea, has recently been reported to exhibit anticancer effects on a number of types of cancer cells in vitro; however, the molecular mechanisms of this anticancer effect remain poorly understood. In the current study, the effects of EGCG on the proliferation and migration of the OVCAR‑3 human ovarian carcinoma cell line were investigated. Cells were treated with EGCG and their proliferation rates were determined by an MTT assay. In addition, cell migration was detected by transwell assay. The activity of mitogen‑activated protein kinases (MAPKs) and the expression of matrix metalloproteinase‑2/9 (MMP‑2/9) were examined by western blotting. The results showed that EGCG significantly inhibited (P<0.05) the proliferation of OVCAR‑3 cells in a time‑ and concentration‑dependent manner. EGCG (100 µM) time‑dependently increased (P<0.05) the activity of p38, but not extracellular signal‑regulated kinases 1/2. SB203580, a specific p38 MAPK inhibitor, completely diminished EGCG‑induced phosphorylation of p38 and partially blocked EGCG‑inhibited OVCAR‑3 cell proliferation. Furthermore, EGCG (0‑100 µM) dose‑dependently inhibited (P<0.05) OVCAR‑3 cell migration. The protein expression levels of MPP‑2, but not MMP‑9, were dose‑dependently decreased following treatment with EGCG (0‑100 µM) for 48 h. These data indicated that EGCG inhibited OVCAR‑3 cell proliferation and migration, potentially mediated via the activation of p38 MAPK and downregulation of the protein expression of MMP2. Thus, the therapeutic potential of EGCG for ovarian cancer requires further investigation.

Invasion and metastasis is the major cause of tumor recurrence, difficulty for cure and low survival rate. Excavating key transcription factors, which can regulate tumor invasion and metastasis, are crucial to the development of therapeutic strategies for cancers. PU.1 is a master hematopoietic transcription factor and a vital regulator in life. Here, we report that, compared to adjacent non-cancerous tissues, expression of PU.1 mRNA in metastatic hepatocellular carcinoma (HCC), but not primary HCC, was significantly down-regulated. In addition, levels of PU.1 mRNA in metastatic hepatoma cell lines MHCC97L and MHCC97H were much lower than in non-metastatic Hep3B cells. Transwell invasion assays after PU.1 siRNA transfection showed that the invasion of hepatoma cell lines was increased markedly by PU.1 knockdown. Oppositely, overexpression of PU.1 suppressed the invasion of these cells. However, knockdown and overexpression of PU.1 did not influence proliferation. Finally, we tried to explore the potential mechanism of PU.1 suppressing hepatoma cell invasion. ChIP-qPCR analysis showed that PU.1 exhibited a high binding capacity with miR-615-5p promoter sequence. Overexpression of PU.1 caused a dramatic increase of pri-, pre-and mature miR-615-5p, as well as a marked decrease of miR-615-5p target gene IGF2. These data indicate that PU.1 inhibits invasion of human HCC through promoting miR-615-5p and suppressing IGF2. These findings improve our understanding of PU.1 regulatory roles and provided a potential target for metastatic HCC diagnosis and therapy.