The role of miR-34c-5p/Notch in epithelial-mesenchymal transition (EMT) in endometriosis.

Endometriosis, a common benign gynecological disease, has the growth characteristics of malignant tumors, however, the pathogenesis of this disease remains unclear. It is well known that micro ribonucleic acids (miRNAs) are involved in epithelial-mesenchymal transition (EMT), associated with the development of endometriosis. This study investigated the role of a specific miRNA, miR-34c-5p, in endometriosis. High-throughput sequencing (HTS) showed that miR-34c-5p expression was reduced in ectopic endometrium (ecEM) in patients from Northeast Asia with ovarian endometriosis. A wound healing assay and a transwell invasion assay showed that miR-34c-5p inhibits the invasion and migration of Ishikawa and End1/E6E7 endocervical cells. Dual luciferase gene reporter assays revealed that miR-34c-5p specifically targets Notch1 3 'UTR, and Western blot analyses showed that miR-34c-5p promotes E-cadherin expression but inhibits Notch1, N-cadherin and vimentin expression in Ishikawa and End1/E6E7 cell lines. These results were reversed following knockdown of miR-34c-5p. Using quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot analyses, there was a significant reduction in the expression of Notch1 in ecEM compared with eutopic endometrium (euEM). The results of this study indicate that miR-34c-5p inhibits the progression of EMT and cell invasion and migration by targeting the Notch signaling pathway, specifically, Notch1. The findings of this study provide unique insights into the development of EMT in endometriosis and novel, potential therapeutic targets.

Luo Y ，Wang D ，Chen S ，Yang Q ... -  《-》

miRNA-1229-5p promotes migration and invasion and suppresses apoptosis of endometrial cells via the STMN1/p38 MAPK axis in endometriosis.

Emerging evidence suggests that aberrantly expressed microRNAs (miRNAs) participate in endometriosis pathogenesis. miR-1229-5p participates in the pathogenesis of several disease, but its precise role and mechanism in endometriosis is unclear. Endometrial tissues were obtained from patients with endometriosis and healthy controls. RT-qPCR and western blotting were employed to detect the expression levels of genes and proteins, respectively. Transcriptome sequencing and luciferase reporter assay were utilized to identify the target of miR-1229-5p. CCK-8, transwell assay, wound healing assay and flow cytometry assay were performed to evaluate the functional roles of miR-1229-5p. Finally, the clinical significance of miR-1229-5p was furtherly analyzed. MiR-1229-5p was upregulated in ectopic endometrium of ovarian endometriosis patients (n = 60) compared to normal endometria of controls (n = 40), and its expression also served as an indicator for endometriosis severity. STMN1 was identified as the target of miR-1229-5p by luciferase experiments, and its expression was significantly downregulated in ectopic endometrium. Functionally, miR-1229-5p overexpression promoted migration, invasion, and inhibited apoptosis of ESCs and Ishikawa cells. Meanwhile, upregulation of miR-1229-5p also facilitated the protein expression of Bcl-2, MMP2, MMP9, N-cadherin, and ZEB1, and repressed the protein levels of Bax and E-cadherin. Whereas downregulation of miR-1229-5p exerted opposite effects. Importantly, STMN1 overexpression could partially reverse the effects of miR-1229-5p upregulation. Mechanistically, miR-1229-5p activates the p38 mitogen-activated protein kinase (p38 MAPK) signaling via targeting STMN1. The newly identified miR-1229-5p-STMN1-p38 MAPK axis illustrates the molecular mechanism of endometriosis progression and offers a potential therapeutic target for treating endometriosis.

Liu L ，Wang L ，Hao N ，Du N ，Li Y ，Kang S ... -  《-》

MiR-21-5p knockdown inhibits epithelial to mesenchymal transition in A549 lung adenocarcinoma cells by upregulating RhoB.

MiR-21-5p is a highly expressed microRNA that plays an important role in various cancer-promoting processes, including anchorage-independent growth, invasion, migration metastasis, and drug resistance in lung cancer. Studies indicate that miR-21-5p may contribute to these processes by promoting epithelial-mesenchymal transition (EMT). Ras homolog gene family member B (RhoB), a gene downregulated by miR-21-5p, has also been linked to EMT in lung cancer. However, the role of the miR-21-5p/RhoB axis in EMT regulation in lung adenocarcinoma remains unclear. In this study, we aimed to investigate the regulatory role of the miR-21-5p/RhoB axis in EMT and related in vitro functional characteristics such as migration, invasion, cisplatin resistance, and the formation of tumor spheroids. A549 cells were transfected with the miR-21-5p inhibitor, RhoB siRNA, and their corresponding negative controls. Wound healing, transwell invasion, Methyl thiazole tetrazolium (MTT), and sphere formation assays were also performed to evaluate the migration, invasion, cisplatin resistance, and anchorage-independent growth of A549 cells. RT-qPCR was used to determine the mRNA expression levels of EMT markers. MiR-21-5p knockdown inhibited migration, invasion, cisplatin resistance, and sphere formation while upregulating E-cadherin and downregulating Slug. Furthermore, RhoB silencing restored EMT and related in vitro functional characteristics in A549 cells. Knockdown of miR-21-5p inhibits EMT and related in vitro functional characteristics by upregulating RhoB, suggesting that miR-21-5p may promote EMT through downregulation of RhoB.

Khair HHA ，Karagöz ID 《-》

MALAT1 promotes epithelial-mesenchymal transition of pancreatic cancer cells through the miR-141-5p-TGF-ß-TGFBR1/TGFBR2 axis.

Li Z ，Yue C ，Hou S ，Huang X ，Wang Z ，Hu W ，Lu H ... -  《-》

Knockdown of circ_0075503 suppresses cell migration and invasion by regulating miR-15a-5p and KLF12 in endometriosis.

Endometriosis is an estrogen-dependent disease. Several researches have reported the dysregulated circular RNAs (circRNAs) in endometriosis, whereas the functions of circRNAs are largely unknown. This study aims to explore the role and mechanism of circ_0075503 in migration and invasion of eutopic endometrial stromal cells. 30 paired ectopic and eutopic endometrium tissues were collected from patients with endometriosis. And primary endometrial stromal cells (ESCs) were stimulated with estradiol (E2) to establish the in vitro cellular model of endometriosis. The levels of circ_0075503, miR-15a-5p and Krüppel-like factor 12 (KLF12) were measured by quantitative reverse transcription polymerase chain reaction or western blot assays. Cell viability, migration and invasion were examined via 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide, transwell assay or western blot assays. The target relationship between miR-15a-5p and circ_0075503 or KLF12 was analyzed by dual-luciferase reporter assay and RNA Immunoprecipitation (RIP) assay. Circ_0075503 expression was elevated in ectopic endometrium and ectopic ESCs. Down-regulation of circ_0075503 suppressed E2-induced promotion of cell viability, migration and invasion in eutopic ESCs. Circ_0075503 could act as a sponge for miR-15a-5p, and KLF12 was targeted by miR-15a-5p. Inhibition of miR-15a-5p reversed the effects of circ_0075503 knockdown on E2-treated ESCs migration and invasion. Besides, miR-15a-5p repressed E2-induced promotion effects on cell migration and invasion via targeting KLF12. Circ_0075503 could regulate KLF12 expression by sponging miR-15a-5p. Knockdown of circ_0075503 inhibited E2-induced enhancement of cell migration and invasion in eutopic ESCs by regulating miR-15a-5p/KLF12 axis, indicating a novel target for the treatment of endometriosis.

Liu D ，Liang Y ，Chen M ，Yang F ，Yao S ... -  《-》