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Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer
Published on: February 9, 2024
miR-144 reverses cisplatin resistance in cervical cancer via targeting LHX2
1Department of Radiation Oncology, First Hospital of Xi'an Jiaotong Univesity, Xi'an, Shaanxi, China.
Abstract:
Mounting evidence showed that microRNAs involve in development and chemoresistance of various human cancers. We explored the roles and mechanisms of miR-144 in resistance to cisplatin (CDDP) of cervical cancer cells. miR-144 and LIM homeobox 2 (LHX2) expression in CDDP-resistant and the parental cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis, respectively. The functions of miR-144 overexpression on cell viability, the incidence of apoptosis, the activity of caspase-3/7, the cleaved-caspase-3 expression, cell migration, and invasion were determined in Hela cells and Hela/CDDP cells. Overexpression of miR-144 reduced cell viability, induced cell apoptosis, and inhibited cell migration and invasion after CDDP treatment. Besides, a luciferase reporter system demonstrated that miR-144 could directly bind to the 3' untranslated region (3'-UTR) of LHX2 messenger RNA (mRNA). Gain expression of miR-144 decreased the expression of LHX2 both in mRNA and protein levels. Furthermore, restoration of LHX2 partly abolished the biological functions of miR-144 in resistance of cervical cancer cells. Taken together, miR-144 overcomes resistance to CDDP via promoting cell apoptosis and inhibiting invasion through targeting LHX2 in cervical cancer cells.
Insights
MicroRNA-144 (miR-144) overcomes cisplatin resistance in cervical cancer by targeting LIM homeobox 2 (LHX2). This enhances apoptosis and reduces invasion, offering a potential therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs play crucial roles in cancer development and chemoresistance.
- Cervical cancer often exhibits resistance to chemotherapy agents like cisplatin (CDDP).
- Understanding the mechanisms of chemoresistance is vital for improving treatment outcomes.
Purpose of the Study:
- To investigate the role and mechanism of microRNA-144 (miR-144) in cisplatin resistance in cervical cancer cells.
- To determine if miR-144 targets LIM homeobox 2 (LHX2) and influences chemoresistance.
- To evaluate the therapeutic potential of modulating miR-144 in cervical cancer.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis were used to measure miR-144 and LHX2 expression.
- Functional assays assessed the impact of miR-144 overexpression on cell viability, apoptosis, and invasion.
- A luciferase reporter assay confirmed the direct binding of miR-144 to the 3'-UTR of LHX2 mRNA.
Main Results:
- Overexpression of miR-144 reduced cell viability, induced apoptosis, and inhibited migration and invasion in cisplatin-treated cervical cancer cells.
- miR-144 directly targets the 3'-untranslated region (3'-UTR) of LIM homeobox 2 (LHX2) mRNA, decreasing its expression.
- Restoration of LHX2 partially reversed the effects of miR-144, indicating its critical role.
Conclusions:
- miR-144 overcomes cisplatin resistance in cervical cancer by targeting and downregulating LHX2.
- This mechanism involves promoting apoptosis and inhibiting invasion.
- miR-144 represents a potential therapeutic target for overcoming chemoresistance in cervical cancer.
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