Epithelial-to-mesenchymal transition (EMT) endows cancer cells with enhanced invasive and metastatic potential during cancer progression. Fractalkine, also known as chemokine (C-X3-C motif) ligand 1 (CX3CL1), the only member recognized so far that belongs to the CX3C chemokine subfamily, was reported to participate in the molecular events that regulate cell adhesion, migration and survival of human prostate cancer cells. However, the relationship between CX3CL1 and EMT remains unknown. We treated DU145 and PC-3 cells with CX3CL1 under hypoxic conditions. The migration and invasion abilities of DU145 and PC-3 cells were detected by Transwell assays. Induction of EMT was verified by morphological changes in the DU145 and PC-3 cells and analysis of protein expression of EMT markers such as E-cadherin and vimentin. To identify the involved signaling pathway in CX3CL1-induced EMT, activation of epidermal growth factor receptor (EGFR) was measured using western blot analysis, and Slug expression was detected with or without an EGFR inhibitor prior to CX3CL1 treatment. Concentrations of soluble and total TGF-α in the CX3CL‑treated DU145 cells were detected by ELISA. Additionally, we determined the involvement of the TACE/TGF-α/EGFR pathway in CX3CL1‑induced EMT using RNA interference and specific inhibitors. CX3CL1 increased the migration and invasiveness of the DU145 and PC-3 cells, and resulted in characteristic alterations of EMT. Our results demonstrated that TACE/TGF-α/EGFR pathway activation and subsequent upregulation of Slug expression were responsible for CX3CL1‑induced EMT, and contributed to the migration and inva-sion of prostate cancer cells. Inhibition of TACE/TGF-α/EGFR signaling reversed EMT and led to reduced migration and invasion abilities of the prostate cancer cells. We provide initial evidence that CX3CL1 exposure resulted in EMT occurrence and enhancement of cell migration and invasion through a mechanism involving activation of TACE/TGF-α/EGFR signaling. These findings revealed that CX3CL1 may serve as a new target for the treatment of prostate cancer.

Background: As an oncogene, long noncoding RNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) can promote tumor metastasis. Hyperexpression of MALAT1 has been observed in many malignant tumors, including hepatocellular carcinoma (HCC). However, the role and mechanism of MALAT1 in HCC remain unclear.Methods: Thirty human HCC and paracancerous tissue specimens were collected, and the human hepatoma cell lines Huh7 and HepG2 were cultured according to standard methods. MALAT1 and Snail family zinc finger (Slug) expression were measured by real‐time PCR, immunohistochemistry, and western blotting. Luciferase reporter assay and RNA immunoprecipitation (RIP) assay verified the direct interaction between miR‐124‐3p and Slug(SNAI2) or MALAT1. Wound healing and transwell assays were performed to examine invasion and migration, and a subcutaneous tumor model was established to measure tumor progression in vivo.Results: MALAT1 expression was upregulated in HCC tissues and positively correlated with Slug expression. MALAT1 and miR‐124‐3p bind directly and reversibly to each other. MALAT1 silencing inhibited cell migration and invasion. miR‐124‐3p inhibited HCC metastasis by targeting Slug.Conclusions: MALAT1 regulates Slug through miR‐124‐3p, affecting HCC cell metastasis. Thus, the MALAT1/miR‐124‐3p/Slug axis plays an important role in HCC.

Transforming growth factor-α (TGF-α) is upregulated in advanced stages of prostate cancer and strongly correlated with metastasis. However, the effect of TGF-α on epithelial-mesenchymal transition (EMT) in prostate cancer and the underlying mechanisms remain unclear. Recently, microRNAs have emerged as new regulators of EMT. This study found that treatment of DU145 cells with TGF-α suppressed the expression of epithelial marker E-cadherin and increased the expression of mesenchymal marker Vimentin as well as changed the cell morphology from cobblestone shape to spindle shape. The level of miR-124 was downregulated by TGF-α in several different cancer cell lines. Enforced expression of miR-124 abolished TGF-α-induced EMT. Slug was proven to be a target of miR-124 and mediated the inhibitory effect of miR-124 on TGF-α-induced EMT. Furthermore, overexpression of miR-124 reduced the migratory and invasive capacity of TGF-α-treated DU145 cells. In conclusion, our findings suggest that miR-124 inhibits TGF-α-induced EMT in DU145 cells by targeting Slug. Thus, miR-124 may be a potential target for prostate cancer therapeutic intervention.

Sensing and responding to endogenous electrical fields are important abilities for cells engaged in processes such as embryogenesis, regeneration and wound healing. Many types of cultured cells have been induced to migrate directionally within electrical fields in vitro using a process known as galvanotaxis. The underlying mechanism by which cells sense electrical fields is unknown. In this study, we assembled a polydimethylsiloxane (PDMS) galvanotaxis system and found that mouse fibroblasts and human prostate cancer PC3 cells migrated to the cathode. By comparing the effects of a pulsed direct current, a constant direct current and an anion-exchange membrane on the directed migration of mouse fibroblasts, we found that these cells responded to the ionic flow in the electrical fields. Taken together, the observed effects of the calcium content of the medium, the function of the store-operated calcium channels (SOCs) and the intracellular calcium content on galvanotaxis indicated that calcium ionic flow from the anode to the cathode within the culture medium permeated the cells through SOCs at the drift velocity, promoting migration toward the cathode. The RTK-PI3K pathway was involved in this process, but the ROCK and MAPK pathways were not. PC3 cells and mouse fibroblasts utilized the same mechanism of galvanotaxis. Together, these results indicated that the signaling pathway responsible for cathode-directed cellular galvanotaxis involved calcium ionic flow from the anode to the cathode within the culture medium, which permeated the cells through SOCs, causing cytoskeletal reorganization via PI3K signaling.

OCT4 is an essential transcription factor for maintaining the self-renewal and the pluripotency of embryonic stem cells (ESCs). The human OCT4 gene can generate three mRNA isoforms (OCT4A, OCT4B and OCT4B1) by alternative splicing. OCT4A protein is a transcription factor for the stemness of ESCs, while the function of OCT4B isoforms remains unclear. Most types of cancer express a relatively low level of OCT4 protein, particularly the OCT4B isoforms. In the present study, we found that OCT4A and OCT4B mRNA were co-expressed in several types of tumor cell lines and tumor samples, and we demonstrated that OCT4B functioned as a non-coding RNA, modulating OCT4A expression in an miRNA-dependent manner [competing endogenous RNA (ceRNA) regulation] at the post-transcription level in the tumor cell lines. This is the first time that ceRNA regulation was observed among spliced isoforms of one gene, and may pave the way for identification of new targets for cancer treatment.