Background: Metastasis of rhabdomyosarcoma (RMS) is the primary cause of tumour-related deaths. Previous studies have shown that overexpression of the guanine nucleotide exchange factor T (GEFT) is correlated with a poorer RMS prognosis, but the mechanism remains largely unexplored. Methods: We focused on determining the influence of the GEFT-Rho-GTPase signalling pathway and the epi-thelialÀmesenchymal transition (EMT) or mesenchymalÀepithelial transition (MET) on RMS progression and metastasis by using RMS cell lines, BALB/c nude mice and cells and molecular biology techniques. Findings: GEFT promotes RMS cell viability, migration, and invasion; GEFT also inhibits the apoptosis of RMS cells and accelerates the growth and lung metastasis of RMS by activating the Rac1/Cdc42 pathways. Interestingly, GEFT upregulates the expression levels of N-cadherin, Snail, Slug, Twist, Zeb1, and Zeb2 and reduces expression level of E-cadherin. Thus, GEFT influences the expression of markers for EMT and MET in RMS cells via the Rac1/Cdc42-PAK1 pathways. We also found that the level of GEFT gene promoter methylation in RMS is lower than that in normal striated muscle tissue. Significant differences were observed in the level of GEFT gene methylation in different histological subtypes of RMS. Interpretation: These findings suggest that GEFT accelerates the tumourigenicity and metastasis of RMS by activating Rac1/Cdc42-PAK signalling pathway-induced EMT; thus, it may serve as a novel therapeutic target.

Rhabdomyosarcoma (RMS) is one of the most common types of soft tissue sarcoma in children; however, the pathogenesis of RMS is unclear. MicroRNAs (miRs) are involved in the development and progression of RMS. The role of miR-410-3p in RMS cell invasion, migration, proliferation and apoptosis, and its possible mechanism were investigated in the current study. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to detect the expression of miR-410-3p in RMS tissues and cells. In addition, the present study investigated the expression levels of molecules associated with the epithelial-mesenchymal transition (EMT), including E-cadherin, N-cadherin, Slug and Snail, and apoptotic factors, including Bcl-2-associated X protein (bax), cleaved-caspase 3, cleaved poly (ADP-ribose) polymerase (PARP), p53 and Bcl-2. Cell Counting Kit-8, terminal deoxynucleotidyl transferase dUTP nick end labeling and Transwell assays were conducted to determine the functional roles of miR-410-3p. Exogenous expression of miR-410-3p inhibited RMS cell invasion, migration and proliferation, induced apoptosis, suppressed the expression of Snail, Slug, N-cadherin and Bcl-2, and increased the expression of E-cadherin, bax, cleaved-caspase 3, cleaved PARP and p53. In summary, it was proposed that miR-410-3p overexpression suppressed invasion, migration and proliferation, downregulated the expression of EMT-associated molecules, and promoted apoptosis and the expression of apoptotic factors in RMS cells. Therefore, miR-410-3p may serve as a novel tumor suppressor gene in RMS, and could possess diagnostic and therapeutic potentials for the treatment of RMS.

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Rationale:Ectopic hamartomatous thymoma is a very rare soft tissue neoplasm that commonly occurs in the lower neck of adult men.Patient concerns:A 32-year-old male presented 1-year history of the tumor lying in left supraclavicular fossa.Diagnoses:Initial consideration of ultrasound and computed tomography was lipoma. After the operation, the pathologist diagnosed it as Ectopic Hamartomatous Thymoma.Interventions:A complete resection was performed.Outcomes:To date, the patient had no evidence of metastasis or recurrence for 26 months after the operation.Lessons:Ectopic hamartomatous thymoma is rare. The mastery of the clinical and pathological features of the disease will contribute to the rapid diagnosis and treatment of the disease. In addition, it can be considered to update the name to “biphenotypic branchioma” in order to avoid conceptual confusion.

Background Guanine nucleotide exchange factor T (GEFT) exhibits high amplification level using high-resolution array comparative genomic hybridization in rhabdomyosarcoma. The overexpression rate of GEFT protein is higher in rhabdomyosarcoma than in normal striated muscle tissues. This study evaluated the aberrant expression of GEFT in multiple subtypes of soft tissue sarcoma (STS) and compared the differences in clinical pathology, histological feature and expression levels of GEFT protein and mRNA between chromosomal translocation-associated sarcomas (CTAS) and non-chromosomal translocation-associated sarcomas (NCTAS). Methods GEFT protein expression was detected using immunohistochemistry (IHC) and tissue microarrays. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to detect the expression of GEFT mRNA. Results The rates of GEFT positive expression (196/219, 89.50%) and overexpression (113/219, 51.60%) were higher in multiple subtypes of STS than in normal striated muscle tissues. The rates of GEFT positive expression and overexpression in all subtypes of STS detected were significantly higher than that in the controls. No difference of GEFT expression was detected between CTAS and NCTAS. Conclusions The abnormal expression of GEFT exists in various subtypes of STS, which may play an important role in tumorigenesis of STS.