Yang Yang

Predictive value of abnormal expression of MPHOSPH9 in reintervention after high intensity focused ultrasound treatment of uterine fibroids

AbstractAimsAberrantly expressed MPHOSPH9 has been reported to be associated with poor prognosis in many diseases. Previous study indicates that MPHOSPH9 is abnormally expressed in patients with uterine fibroids (UFs). This study focused on the possible prognostic value of MPHOSPH9 in UFs patients after high intensity focused ultrasound (HIFU) treatment.MethodsA total of 455 UFs patients participated in the study, including 95 patients who needed reintervention (Reintervention group) and 360 patients who did not need reintervention (Non‐reintervention group) after HIFU treatment. They volunteered blood samples before HIFU treatment. The relative expression of MPHOSPH9 was assessed by qRT‐PCR. Cox regression analysis was performed to assess the prognostic value of MPHOSPH9 and risk factors of postoperative reintervention.ResultsThe expression of MPHOSPH9 was markedly elevated in Reintervention, compared to that of the Non‐reintervention group (p < 0.001). Five‐year follow‐up results showed that among these postoperative patients, 95 patients required reintervention and the reintervention time mainly occurred during 10–40 months after surgery. The Cox regression analysis demonstrated that UFs size (hazard ratio = 2.769, 95% confidence interval: 1.366–5.610) and the high MPHOSPH9 expression level (hazard ratio = 3.160, 95% confidence interval: 1.506–6.630) were independent risk factors for postoperative reintervention.ConclusionsThe enhanced MPHOSPH9 was a potential candidate for predicting postoperative reintervention in UFs patients.

GSK3B inhibition reduced cervical cancer cell proliferation and migration by modulating the PI3K/Akt signaling pathway and epithelial-to-mesenchymal transition

Previous studies show that glycogen synthase kinase 3β (GSK3B) plays an important role in tumorigenesis. However, its role in cervical cancer is unclear. The present study silenced GSK3B with siRNAs and/or chemical inhibitors to determine its role in HeLa cervical cancer cell proliferation and migration as well as in xenograft tumor growth. Cell Counting Kit (CCK)-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to determine cell survival and proliferation. Scratch and Transwell® assays were used to evaluate cell migration. Xenograft tumors were used to evaluate the effect of GSK3B on tumor growth. Transcriptomic sequencing was used to clarify the mechanisms underlying the foregoing processes. Public databases and clinical specimens showed that GSK3B was upregulated in cervical cancer tissues and correlated with poor prognosis. In vitro experiments indicated that GSK3B inhibition reduced cell viability, proliferation, and migration. In vivo experiments demonstrated that GSK3B inhibition slowed xenograft tumor growth. Transcriptomic sequencing revealed that GSK3B inhibition modulated the phosphatidylinositol 3-carboxykinase (PI3K)/protein kinase B (Akt) and extracellular matrix (ECM)-receptor interaction signaling pathways. GSK3B inhibition decreased the protein levels of phosphorylated PI3K and Akt and the levels of mesenchymal markers but increased those of epithelial markers. An activator of the PI3K/Akt signaling pathway counteracted the suppressive effects of GSK3B inhibition on HeLa cell viability and proliferation and on PI3K/Akt signaling. Our data suggested that GSK3B regulated cervical cancer cell proliferation and migration by modulating the PI3K/Akt signaling pathway and epithelial-to-mesenchymal transition (EMT).