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Jaceosidin inhibits the progression and metastasis of NSCLC by regulating miR-34c-3p/Integrin α2β1 axis
Qiao-Ru Guo1, Wen-Min Zhou1, Guo-Bin Zhang1
1Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China.
Abstract:
Non-coding RNAs are crucial for cancer progression, among which miR-34c-3p has been demonstrated to be a tumor suppressor in non-small cell lung cancer (NSCLC). In this study, we attempt to identify flavonoids that can up-regulate miR-34c-3p expression, evaluate the anticancer activity of the flavonoids and explore its underlying mechanism in NSCLC cells. Six flavonoids were screened by RT-qPCR and we found that jaceosidin significantly increased miR-34c-3p expression in A549 cells. We found that jaceosidin inhibited the proliferation, migration and invasion of A549 and H1975 cells in a dose-relevant manner, indicated by cell counting kit (CCK-8) assay, wound healing assay, transwell assay and EdU assay, we observed that jaceosidin inhibited the proliferation, migration and invasion of A549 and H1975 cells in a dose-relevant manner. Further research suggested that miR-34c-3p bound to the transcriptome of integrin α2β1 and then inhibited its expression, leading to the inhibitory effect on the migration and invasion of NSCLC. Our study sheds some light on anti-tumor of jaceosidin and provides a potential lead compound for NSCLC therapy.
Insights
Jaceosidin, a flavonoid, boosts miR-34c-3p expression, suppressing non-small cell lung cancer (NSCLC) cell proliferation, migration, and invasion by targeting integrin α2β1.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Non-coding RNAs, including microRNAs (miRNAs), play significant roles in cancer development.
- miR-34c-3p acts as a tumor suppressor in non-small cell lung cancer (NSCLC).
- Identifying natural compounds that modulate miRNA expression is a promising therapeutic strategy.
Purpose of the Study:
- To screen for flavonoids that up-regulate miR-34c-3p expression in NSCLC cells.
- To evaluate the anticancer effects of identified flavonoids.
- To elucidate the underlying molecular mechanism of action.
Main Methods:
- Reverse transcription quantitative polymerase chain reaction (RT-qPCR) for gene expression analysis.
- Cell proliferation assays (CCK-8, EdU).
- Cell migration and invasion assays (wound healing, Transwell).
Main Results:
- Jaceosidin significantly increased miR-34c-3p expression in A549 cells.
- Jaceosidin inhibited proliferation, migration, and invasion of NSCLC cells (A549 and H1975) in a dose-dependent manner.
- miR-34c-3p was found to target integrin α2β1, inhibiting its expression and consequently suppressing NSCLC cell migration and invasion.
Conclusions:
- Jaceosidin exhibits significant anticancer activity against NSCLC.
- The mechanism involves up-regulation of miR-34c-3p, which targets integrin α2β1.
- Jaceosidin represents a potential therapeutic lead compound for NSCLC treatment.
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