MicroRNA-324-5p affects the radiotherapy response of cervical cancer via targeting ELAV-like RNA binding protein 1.

Cervical cancer (CC) seriously threatens the health of women. Radiation therapy (RT) is the major treatment for CC. However, the recurrent CC can acquire resistance to RT. Thus, it is necessary to find a new method for reversing RT resistance in CC. It has been reported that miR-324-5p can suppress the progression of multiple cancers. However, whether it can reverse resistance to RT in CC remains unclear. qRT-PCR and Western blotting were used to detect gene and protein expression in CC cells, respectively. Cell proliferation was tested by CCK-8 assay and colony formation assay. In addition, cell apoptosis was detected by flow cytometry. Transwell assays were performed to detect cell migration. Dual luciferase reporter assay and TargetScan were used to explore the targets of microRNA-324-5p (miR-324-5p). MiR-324-5p was downregulated in CC cells. Overexpression of miR-324-5p sensitized CC cells to RT. In addition, miR-324-5p mimics significantly induced apoptosis and inhibits the migration of CC cells in the presence of 137 Cs ionizing radiation. Furthermore, miR-324-5p sensitized CC cells to ionizing radiation by targeting ELAV-like RNA binding protein 1 (ELAVL1). MiR-324-5p overexpression affects the radiotherapy response of CC by targeting ELAVL1, which may serve as a new target for the treatment of CC.

Dusp6 inhibits epithelial-mesenchymal transition in endometrial adenocarcinoma via ERK signaling pathway.

Background Endometrial adenocarcinoma (EAC) is one of the most commonly diagnosed gynaecological malignancies among female population of the developed countries. DUSP6 is a negative regulator of ERK signaling, which is a molecular switch involved in MAPK signaling during the progress of malignancies. DUSP6 was previously found to inhibit tumorigenesis and EMT-associated properties in several cancers, however, its exact role in EAC remains unclear Methods The level of DUSP6, (E-cad) and (N-cad) in EAC cancerous tissues and respective adjacent non-cancerous tissues were examined by western-blot or immunohistochemistry. The cell growth, invasion and migration abilities were measured in Ishikawa 3H12 endometrial cancer cell lines with overexpressed or knock down DUSP6. Protein levels of EMT-associated markers E-cadherin, N-cadherin and Vimentin were also determined. The impacts of DUSP6 on ERK signaling was assessed by detection of ERK and p-ERK. Results Down-regulation of DUSP6 was observed in EAC compared with the normal controls. The overexpression of DUSP6 significantly attenuated tumor cell growth, invasion, migration abilities and inhibited EMT-associated markers, while knock down of DUSP6 showed opposite trends. Overexpression of DUSP6 also down-regulated p-ERK and the knock down of DUSP6 inversely up-regulated p-ERK level. Conclusions DUSP6 inhibited cell growth, invasion and migration abilities in Ishikawa 3H12 cells as well as attenuating EMT-associated properties. This tumor suppressive effect of DUSP6 in EAC is achieved by inhibiting ERK signaling pathway.

Long non-coding RNA SPRY4-IT1 promotes epithelial-mesenchymal transition of cervical cancer by regulating the miR-101-3p/ZEB1 axis.

BACKGROUND: Emerging evidences have indicated that long non-coding RNAs (LncRNAs) play vital roles in cancer development and progression. Previous studies have suggested that overexpression of SPRY4 intronic transcript 1 (SPRY4-IT1) predicates poor prognosis and promotes tumor progress in cervical cancer (CC). However, the underlying mechanism of SPRY4-IT1 in CC remains unknown. The aim of the present study is to evaluate the function and mechanism of SPRY4-IT1 in CC. METHODS: SPRY4-IT1 was detected by quantitative PCR. Wound-healing assay and Transwell assay were performed to detect cell migration and invasion, respectively. Western blotting assays were used to analyze the protein expression of E-cadherin, N-cadherin and vimentin. Tumor xenografts experiments were performed to detect the effect of SPRY4-IT1 in vivo. Dual luciferase reporter assay was used to investigate potential molecular mechanism of SPRY4-IT1 in CC cells. RESULTS: SPRY4-IT1 was up-regulated in CC cell lines. Knockdown of SPRY4-IT1 significantly inhibited CC cells migration and invasion in vitro and in vivo Moreover, knockdown of SPRY4-IT1 significantly suppressed the epithelial-mesenchymal transition (EMT) of CC by increased E-cadherin expression and decreased the N-cadherin and vimentin expression. Mechanically, SPRY4-IT1 could directly bind to miR-101-3p and effectively act as a competing endogenous RNA (ceRNA) for miR-101-3p to regulate the expression of the target gene ZEB1Conclusions: Our findings indicate that the SPYR4-IT1/miR-101-3p/ZEB1 axis contributes to CC migration and invasion, which may provide novel insights into the function of lncRNA-driven tumorigenesis of CC.