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Published on: August 2, 2024
Long non‑coding RNA MCM3AP‑AS1 drives ovarian cancer progression via the microRNA‑143‑3p/TAK1 axis
Jihong Wen1, Shumei Han1, Man Cui1
1Department of Gynecology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Abstract:
The long non‑coding RNA (lncRNA) MCM3AP antisense 1 (MCM3AP‑AS1) has previously been shown to be a key regulator of multiple types of cancer; however whether it is important in the context of ovarian cancer (OC) is uncertain. The present study determined that MCM3AP‑AS1 expression in samples from patients with OC was significantly increased, and was associated with tumor stage, presence of lymph node metastases and poorer overall survival. The role of this lncRNA was investigated in vitro, and it was observed that knockdown of MCM3AP‑AS1 impaired OC cell proliferation, migration and colony formation. Similarly, it disrupted tumor growth in vivo. The present study further determined that MCM3AP‑AS1 was able to directly interact with microRNA (miRNA or miR)‑143‑3p as a competing endogenous (ce)RNA for this miRNA, thereby regulating the expression of transforming growth factor‑β‑activated kinase 1 (TAK1), a known target of miR‑143‑3p in OC. Consistent with this, inhibition of miR‑143‑3p was sufficient to partially reverse the effects of MCM3AP‑AS1‑knockdown, which inhibited the proliferation, migration and invasion of OC cells. Together, these results indicate that MCM3AP‑AS1 serves as an oncogenic lncRNA in OC by binding to miR‑143‑3p and thereby promoting TAK1 expression, and suggest that this lncRNA may be a possible target for therapy in OC.
Insights
The long non-coding RNA MCM3AP-AS1 is elevated in ovarian cancer (OC) and promotes tumor growth by interacting with miR-143-3p. This interaction upregulates TAK1, suggesting MCM3AP-AS1 as a potential therapeutic target for OC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer.
- The specific role of MCM3AP antisense 1 (MCM3AP-AS1) in ovarian cancer (OC) remains unclear.
- Previous studies implicated MCM3AP-AS1 in various cancers, necessitating investigation in OC.
Purpose of the Study:
- To investigate the expression and function of MCM3AP-AS1 in ovarian cancer.
- To elucidate the molecular mechanism underlying MCM3AP-AS1's role in OC progression.
- To assess the potential of MCM3AP-AS1 as a therapeutic target in OC.
Main Methods:
- Quantitative real-time PCR to measure MCM3AP-AS1 expression in OC tissues.
- In vitro assays (cell proliferation, migration, colony formation) following MCM3AP-AS1 knockdown.
- In vivo tumor growth assays in a mouse model.
- RNA immunoprecipitation and luciferase reporter assays to confirm MCM3AP-AS1 interaction with miR-143-3p.
- Western blotting to assess TAK1 expression.
Main Results:
- MCM3AP-AS1 expression was significantly upregulated in OC tissues and correlated with advanced tumor stage, lymph node metastasis, and poorer survival.
- Knockdown of MCM3AP-AS1 inhibited OC cell proliferation, migration, colony formation, and tumor growth in vivo.
- MCM3AP-AS1 directly binds to miR-143-3p, acting as a competing endogenous RNA (ceRNA).
- This interaction leads to increased expression of transforming growth factor-β-activated kinase 1 (TAK1) in OC cells.
- Inhibition of miR-143-3p partially reversed the effects of MCM3AP-AS1 knockdown on OC cell proliferation, migration, and invasion.
Conclusions:
- MCM3AP-AS1 acts as an oncogenic lncRNA in ovarian cancer.
- It promotes OC progression by sponging miR-143-3p and subsequently increasing TAK1 expression.
- MCM3AP-AS1 represents a promising therapeutic target for ovarian cancer treatment.
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