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- Title
Elevated phosphatase of regenerating liver 3 (PRL-3) promotes cytoskeleton reorganization, cell migration and invasion in endometrial stromal cells from endometrioma.
- Authors
Hong Zhan; Junyan Ma; Fei Ruan; Bedaiwy, Mohamed A.; Bo Peng; Ruijin Wu; Jun Lin; Zhan, Hong; Ma, Junyan; Ruan, Fei; Peng, Bo; Wu, Ruijin; Lin, Jun
- Abstract
<bold>Study Question: </bold>Is phosphatase of regenerating liver-3 (PRL-3) associated with increased motility of endometriotic cells from endometrioma?<bold>Summary Answer: </bold>Elevated PRL-3 promotes cytoskeleton reorganization, cell migration and invasion of endometrial stromal cells (ESCs) from endometrioma.<bold>What Is Known Already: </bold>Overexpression of PRL-3 is associated with cancer cell migration, invasion and metastatic phenotype.<bold>Study Design, Size, Duration: </bold>Primary human ESCs were isolated from eutopic endometrium of women without endometriosis (EuCo, n = 10), with histologically proven endometrioma (EuEM, n = 19) and from the cyst wall of ovarian endometriosis (OvEM, n = 26).<bold>Participants/materials, Setting, Methods: </bold>The expression of PRL-3 in ESCs derived from EuCo, EuEM and OvEM at different phases of menstrual cycle were compared. The protein and mRNA levels of PRL-3 were examined by western blot and RT-qPCR, respectively. ESCs from OvEM were transfected with/without short hairpin RNA (shRNA) or small interfering RNA (siRNA). Additionally, a plasmid-mediated delivery system was used to achieve PRL-3 overexpression in ESCs from EuEM. The cellular distribution of F-actin and α-tubulin were examined by immunocytochemistry. Cell motility was evaluated by a transwell migration/invasion assay.<bold>Main Results and the Role Of Chance: </bold>The protein and mRNA levels of PRL-3 are significantly elevated in ESCs from OvEM compared with EuCo and EuEM. The expression of PRL-3 was not altered between proliferative phase and secretory phase in ESCs from all groups. Knockdown of PRL-3 significantly modified the distribution of F-actin and α-tubulin cytoskeleton, inhibited cell migration and invasion. Endogenous inhibition of PRL-3 attenuated the expression of Ras homolog gene family members A and C (RhoA, RhoC), Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) and matrix metalloproteinase (MMP) 9, but not MMP2 in ESCs from OvEM. Additionally, overexpression of PRL-3 in ESCs from EuEM up-regulates cell migration and invasion, and increases the expression of RhoA, RhoC, ROCK1 and MMP9.<bold>Limitations, Reasons For Caution: </bold>Lack of in vivo animal studies is the major limitation of our report. Our results should be further confirmed in a larger cohort of patients and extended to include eutopic and ectopic endometrium from patients with peritoneal endometriosis at different stages of the disease.<bold>Wider Implications Of the Findings: </bold>Our study describes that elevated expression of PRL-3 contributes to the cell motility of ESCs from endometrioma. The results emphasize the importance of metastatic-related factor PRL-3 in the pathogenesis of endometrioma.<bold>Study Funding/competing Interest: </bold>This work was supported by National Natural Science Foundation of China (No. 81170546) and Zhejiang Medicine Science and Technology Projects (No. Y13H040003). The authors declare no conflict of interest.
- Subjects
PHOSPHATASES; LIVER regeneration; CYTOSKELETON; CELL migration; ENDOMETRIAL diseases; PROTEIN metabolism; RNA metabolism; CARRIER proteins; CELL culture; CELL motility; COMPARATIVE studies; CONNECTIVE tissue cells; CYTOPLASM; ENDOMETRIOSIS; ENDOMETRIUM; ESTERASES; GENES; RESEARCH methodology; MEDICAL cooperation; MENSTRUAL cycle; OVARIAN diseases; PHOSPHOTRANSFERASES; PROTEINS; PROTEOLYTIC enzymes; RECOMBINANT proteins; RESEARCH; EVALUATION research; CHEMICAL inhibitors
- Publication
Human Reproduction, 2016, Vol 31, Issue 4, p723
- ISSN
0268-1161
- Publication type
journal article
- DOI
10.1093/humrep/dew015