ArticleAmerican journal of translational research2021
LASS2 mediates Nrf2-driven progestin resistance in endometrial cancer.
Article in American journal of translational research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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Who cites it
10 citing papers in PubMed, 8 citations in OpenAlex.
- Ceramide: a pivotal lipid mediator shaping female reproductive homeostasis and pathophysiology.Journal of ovarian research · 2026Review
- Mitochondrial Long Non-Coding RNAs in Gynecological Cancers: Pathogenic Signaling Pathways and Therapeutic Opportunities.Current issues in molecular biology · 2026Review
- Oxidative stress as a nexus: Integrating mitophagy and ferroptosis in endometrial carcinogenesis (Review).Oncology letters · 2026Review
- Role of TPD52 in Endometrial Cancer: Impact on EMT and the PI3K/AKT and ERK/MAPK Signaling.Protein and peptide letters · 2025Article
- Article
- Ceramide kinase-mediated C1P metabolism attenuates acute liver injury by inhibiting the interaction between KEAP1 and NRF2.Experimental & molecular medicine · 2024Article
- TRPS1 regulates the opposite effect of progesterone via RANKL in endometrial carcinoma and breast carcinoma.Cell death discovery · 2023Article
- Progestin Resistance and Corresponding Management of Abnormal Endometrial Hyperplasia and Endometrial Carcinoma.Cancers · 2022Review
- Investigation of Molecular Features Involved in Clinical Responses and Survival in Advanced Endometrial Carcinoma Treated by Hormone Therapy.Journal of personalized medicine · 2022Article
- LASS2 impairs proliferation of glioma stem cells and migration and invasion of glioma cells mainly via inhibition of EMT and apoptosis promotion.Journal of Cancer · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Progestin administration serves as the optimal conservative treatment method for women with endometrial cancer or precancer lesions who want to preserve fertility. However, there are still at least 30% of patients in which progestin resistance occurs. LASS2 (Ceramide Synthase 2) has been reported to be involved in chemotherapy resistance, whether it also plays a role in progestin resistance is not clear. Here, we explored the detailed mechanism by which Nrf2/LASS2 contributes to progestin resistance and disease progression.
methodsIHC assays were performed to estimate the expression pattern of Nrf2 and LASS2. Moreover, it bears three antioxidant response elements (ARE) in the promoter region of LASS2 gene, therefore, Luciferase assays were performed to determine if Nrf2 regulates LASS2 by binding with these ARE sequence. Western Blot assays were used to determine the expression of Nrf2 and LASS2 protein among various endometrial cell lines. Relative mRNA expression levels were detected by RT-PCR. Cellular growth was monitored with CCK-8 tests. Apoptosis was determined with Annexin V-PI staining and flow cytometry analysis. siRNA knockdown was performed to investigate the effects of Nrf2 on cell proliferation.
resultNrf2/LASS2 is highly expressed in endometrial cancer tissue, as compared to expression levels in normal endometrial tissue. Proliferation assays demonstrated that overexpression of Nrf2/LASS2 resulted in progestin resistance. Conversely, knockdown of LASS2 increased apoptosis and decreased cell viability. In addition, metformin overcame progestin resistance by down-regulating Nrf2/LASS2 expression.
conclusionOur findings provide new insight into the mechanism of progestin resistance in type I endometrial cancer. Nrf2/LASS2 may not only be a possible marker for predicting the prognosis of endometrial cancer but also serve as a potential therapeutic target.
Indexed as
Identifiers
33841656PMC8014362W3154075392What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.