Erratum: [Corrigendum] MicroRNA­23a inhibits endometrial cancer cell development by targeting SIX1.

[This corrects the article DOI: 10.3892/ol.2019.10694.].

CYPA promotes the progression and metastasis of serous ovarian cancer (SOC) in vitro and in vivo.

Ovarian cancer (OC) is a type of gynaecological malignancy with high mortality in females. Serous ovarian cancer (SOC) is a distinct subtype of OC with poor early diagnosis. Given the limitations of traditional therapies, such as chemotherapy, targeted treatment is therefore a promising therapy to improve the survival rate of SOC patients. Cyclophilin A (CYPA) is a member of Cyclophilin family and thought to participates in multiple cellular processes such as cell transduction and immune modulation. Recently, various of studies indicated that CYPA has critical impact on cancer progression. CYPA could regulate cell proliferation, invasion, and chemoresistance of multiple types of cancers. However, it is still unclear whether it could affect ovarian cancer. In this study, we demonstrated that CYPA was highly expressed in SOC tissues compared with adjacent tissues. Further, CYPA was significantly associated with clinical stage and lymphnode metastasis of SOC patients. Additionally, data indicated that knockdown of CYPA by its shRNA dramatically reduces migration and invasion capacity of SOC cells in vitro and blocks tumor metastasis in vivo. Our study investigates the involvement of CYPA in the progression and metastasis of SOC, and therefore provides CYPA as a promising therapeutic target for SOC treatment.

MicroRNA-23a inhibits endometrial cancer cell development by targeting SIX1.

The present study focused on exploring the inhibitory mechanism of microRNA (miR)-23a in endometrial cancer. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to investigate miR-23a expression in endometrial tissues and endometrial cancer cells. A colony formation assay using crystal violet staining was performed to compare cell proliferation, while wound-healing and Transwell assays were performed to compare cell migration and invasion. Subsequently, bioinformatics and a luciferase reporter gene assay were used to investigate the effect of miR-23a on sine oculis homeobox homolog 1 (SIX1) expression, and the biological function of SIX1 was analyzed. Additionally, a nude mouse tumorigenicity assay was performed to test the inhibitory effect of miR-23a and Taxol® therapy in endometrial cancer. Finally, immunohistochemistry and RT-qPCR were used to explore the association between miR-23a and SIX1 expression in endometrial cancer tissues. miR-23a was underexpressed in endometrial cancer tissues compared with in para-carcinoma tissues, and the overexpression of miR-23a inhibited proliferation and invasion of endometrial cancer cells. Furthermore, SIX1 was demonstrated to be a downstream target of miR-23a, and miR-23a reduced SIX1 expression. Additionally, SIX1 inversely promoted cell proliferation, migration and invasion. In addition, the effects of reduced cell proliferation and increased cell invasion following miR-23a overexpression could be reversed by adding SIX1 to in vitro culture. Furthermore, the inhibitory effect of miR-23a and Taxol therapy, which reduced SIX1 expression in endometrial cancer, was demonstrated in vivo. Finally, a negative association between miR-23a and SIX1 expression was demonstrated in endometrial cancer tissues. The results of the present study revealed that miR-23a may inhibit endometrial cancer development by targeting SIX1.

[Role of epidermal growth factor signaling system in the pathogenesis of endometriosis under estrogen deprivation conditions].

OBJECTIVE: To study the role of epidermal growth factor (EGF) , epidermal growth factor receptor(EGFR), extracellular signal-regulated kinase 1/2 (p-ERK1/2) in the pathogenesis of endometriosis under estrogen deprivation conditions. METHODS: The estrogen was quickly-stripped in medium and the female nude mice were castrated by bilateral oophorectomy to build estrogen deprivation in vitro and in vivo experimental models, respectively. (1) In vitro experiments:according to different treatments the estrogen deprived ectopic endometrial cells were classified into 4 groups: a. EGF group:the ectopic endometrial cells were cultured for 72 hours with different concentrations of EGF (0.01, 0.1, 1, 10, 50, 100 ng/ml), the results of EGF group were represented by the result of cells treated by 10 ng/ml EGF cultured for 72 hours; b. EGF+PD98059 group:the ectopic endometrial cells were cultured for 72 hours with 5×10(-2) mol/L PD98059 (inhibitor of ERK), followed by a cultivation for 72 hours treated by 10 ng/ml EGF+5×10(-2) mol/L PD98059; c. EGF+ ICI182780 group: the ectopic endometrial cells were cultured for 72 hours with 10(-6) mol/L ICI182780 [inhibitor of estrogen receptor(ER)], followed by a cultivation for 72 hours treated by 10 ng/ml EGF+10(-6) mol/L ICI182780; d. Blank control group:the ectopic endometrial cells were cultured with no treatment. The proliferation activity of ectopic endometrial cells in all groups after treatment were examined by methyl thiazolyl tetrazolium (MTT) method represented by absorbance value (A). The expression of p-ERK1/2 protein were detected by western blot. (2) In vivo experiments: 64 female nude mice were randomly divided into control and castration groups (both n=32) using random number chart. The mice in castration group were castrated by bilateral oophorectomy on 3 weeks after the endometriosis model was established. The levels of EGF, EGFR, p-ERK1/2 protein in ectopic lesions of both groups were measured on 4, 6, 8 and 10 weeks after the endometriosis model was established by western blot. RESULTS: (1) The proliferation activity of ectopic endometrial cells:the proliferation activity of ectopic endometrial cells treated by different concentrations of EGF (0.01, 0.1, 1, 10, 50, 100 ng/ml) for 72 hours were 0.310±0.010, 0.340±0.020, 0.670±0.010, 0.980±0.030, 1.360±0.020, 1.670±0.020, respectively, the proliferation activity was increased along with of EGF concentrations.The proliferation activity was 0.680±0.030 at EGF+ PD98059 group, the differences exhibited significant difference when compared with that at EGF group with 100 ng/ml for 72 hours (P<0.01) .The proliferation activity of EGF+ ICI182780 and blank control groups were 0.330±0.030 and 0.310±0.030, respectively, which did not reached statistical differences (P>0.05). (2) The expression of EGF, EGFR, pERK1/2 protein: a. In vitro experiments:the levels of p-ERK1/2 protein in EGF and blank control groups were 0.670±0.020 and 0.600±0.010, respectively, which reached statistical differences (P<0.05). The level of p-ERK1/2 protein in EGF+ PD98059 group was 0.610±0.020, which exhibited significant differences with that at blank control group (P>0.05). b. In vivo experiments:at 4, 6 and 8 weeks after the endometriosis models were established, the expression of EGF protein in the ectopic lesions of castration group and control group were (0.530±0.015 versus 0.610±0.015), (0.400±0.029 versus 0.620±0.018), (0.560±0.026 versus 0.630±0.021), respectively, the levels of EGFR protein were (0.500±0.030 versus 0.640±0.030), (0.470±0.020 versus 0.630±0.020), (0.510±0.030 versus 0.610±0.020) respectively, and the level of p-ERK1/2 protein were (0.500±0.020 versus 0.580±0.020), (0.490±0.020 versus 0.580±0.020), (0.570±0.020 versus 0.590±0.020), respectively. The difference of EGF, EGFR, p-ERK1/2 protein expression levels between two groups did not exhibited significant difference (P<0.01, P<0.01, P<0.05). At 10 weeks after the endometriosis models were established, the levels of EGF protein in castration group and control group were both 0.620±0.020, the levels of EGFR protein were both 0.610±0.020, and the level of p-ERK1/2 protein were 0.590±0.010 and 0.600±0.020. No statistical difference (P>0.05) was found between those two groups (P>0.05). CONCLUSIONS: EGF could stimulate the proliferation of ectopic endometrial cells by activating the ERK pathway under estrogen deprivation conditions. The inhibition of EGF signaling system in ectopic lesions was alleviated along with the prolongation of the period of estrogen deprivation.

MicroRNA-182 promotes cell growth, invasion, and chemoresistance by targeting programmed cell death 4 (PDCD4) in human ovarian carcinomas.

As an important tumor suppressor, programmed cell death 4 (PDCD4) influences transcription and translation of multiple genes, and modulates different signal transduction pathways. However, the upstream regulation of this gene is largely unknown. In this study, we found that microRNA-182 (miRNA-182, miR-182) was upregulated, whereas PDCD4 was downregulated in ovarian cancer tissues and cell lines. Blocking or increase of miR-182 in ovarian cancer cell lines led to an opposite alteration of endogenous PDCD4 protein level. Using fluorescent reporter assay, we confirmed the direct and negative regulation of PDCD4 by miR-182, which was dependent on the predicted miR-182 binding site within PDCD4 3' untranslated region (3' UTR). MTT and colony formation assays suggested that miR-182 blockage suppressed, whereas miR-182 mimics enhanced viability and colony formation of ovarian cancer cells. These effects may partly be attributed to the cell cycle promotion activity of miR-182. miR-182 also contributed to migration and invasion activities of ovarian cancer cells. Furthermore, miR-182 reduced the chemosensitivity of ovarian cancer cells to CDDP and Taxol, possibly by its anti-apoptosis activity. Importantly, all the alterations of the above cellular phenotypes by blocking or enhancing of miR-182 could be alleviated by subsequent suppression or ectopic expression of its target PDCD4, respectively. We conclude that in ovarian cancer cells, miR-182 acts as an oncogenic miRNA by directly and negatively regulating PDCD4.