Abstract
ObjectiveThe curative effect of high-efficiency progesterone and other therapeutic drugs for endometrioid adenocarcinoma patients with preservation of reproductive capacity has not been satisfactory so far. Novel therapeutic drugs need to be explored.MethodsWe investigated the cytoplastic and nuclear expression levels of LMTK3 between endometrioid adenocarcinoma tissues and adjacent endometrial tissues by immunohistochemistry. We detected the effects of LMTK3 on cell viability of Ishikawa cells by CCK-8. We detected the effects of LMTK3 on cell cycle and apoptosis of Ishikawa cells by flow cytometry. We also detected the effects of LMTK3 knockdown on mRNA and protein levels of ERα by qRT-PCR and western blotting, respectively. We also used the cBioPortal online database to analyze the coexpression of LMTK3 and ESR1 in 1647 UCEC samples.ResultsWe used TMAs to identify that LMTK3 was mainly detected in the cytoplasm of endometrioid tissues, and cytoplasmic LMTK3 expression in endometrioid tissues was higher than that in adjacent endometrial tissues (P < 0.05). LMTK3 knockdown decreased the proliferation of Ishikawa cells through decreasing cell viability (P < 0.01), increasing G1 (P < 0.001) arrest, and promoting apoptosis (P < 0.01). There was a positive correlation between the mRNA expression levels of LMTK3 and ESR1 (Spearman: P=2.011e-5, R=0.13; Pearson: P=7.18e-8, R=0.17). Knockdown of LMTK3 also reduced the mRNA (P < 0.001) and protein (P < 0.001) levels of ERα.ConclusionsInhibitors of LMTK3 may be a possible future treatment for ERα and LMTK3 highly expressed endometrioid adenocarcinoma following appropriate studies.
Highlights
Uterine corpus endometrial carcinoma (UCEC) is the second most common malignant tumor of the female reproductive system in China [1] and the first in the United States; there were 65,620 estimated new cases and 12,590 estimated deaths in 2020 in the United States [2]
The results indicated that the early apoptosis rate of Ishikawa cells transfected with a control siRNA plasmid was only 4.31 ± 0.60%, and that of Ishikawa cells transfected with plasmid siLMTK3 was increased to 7.08 ± 0.61% (P
We used bioinformatics methods to explore the positive correlation between the mRNA expression of LMTK3 and ESR1 in 1,647 UCEC samples, and we found that LMTK3 knockdown really reduced the mRNA and protein levels of ERa
Summary
Uterine corpus endometrial carcinoma (UCEC) is the second most common malignant tumor of the female reproductive system in China [1] and the first in the United States; there were 65,620 estimated new cases and 12,590 estimated deaths in 2020 in the United States [2]. A meta-analysis of 27 studies showed that the complete remission rate after oral progesterone treatment was 76.3%, the complete remission rate after intrauterine progesterone treatment was 72.9%, and the pregnancy rate after oral progesterone treatment was 52.1% [7]. A meta-analysis of 32 studies showed that the recurrence rate of progesterone treatment was 41%, and the recurrence rate continued to increase at least within 5 years; the live birth rate after progesterone treatment was 28% [8]. Another retrospective study mentioned that the recurrence rate after oral progesterone treatment was 81.8%, and the pregnancy rate after high-dose progesterone treatment was only 6.3% [9]. Looking for new therapeutic targets and developing highly effective molecular targeted drugs with less side effects have become the focus of fertility preservation research and the key to success of fertility preserving therapy for EEC patients
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