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Published on: March 30, 2019
The Pathway Analysis of Micrornas Regulated Drug-Resistant Responses in HeLa Cells
Abstract:
Chemotherapy is the main strategy in the treatment of cancer; however, the development of drug-resistance is the obstacle in long-term treatment of cervical cancer. Cisplatin is one of the most common drugs used in cancer therapy. Recently, accumulating evidence suggests that miRNAs are involved in various bioactivities in oncogenesis. It is not unexpected that miRNAs play a key role in acquiring of drug-resistance in the progression of tumor. In this study, we induced and maintained four levels of cisplatin-resistant HeLa cell lines (HeLa/CR1, HeLa/CR2, HeLa/CR3, and HeLa/CR4). According to the previous studies and existing evidence, we selected five miRNAs (miR-183, miR-182, miR-30a, miR-15b, and miR-16) and their potential target mRNAs as our research targets. The real-time RT-PCR was adopted to detect the relative expression of miRNAs and their mRNAs. The results show that miR-182 and miR-15b were up-regulated in resistant cell lines, while miR-30a was significantly down-regulated. At the same time, their targets are related to drug resistance. Compared to their parent HeLa cell line, the expression of selected miRNAs in resistant cell lines altered. The alteration suggests that HeLa cell drug resistance is associated with distinct miRNAs, which indicates that miRNAs may be one of the therapy targets in the treatment of cervical cancer by sensitizing cell to chemotherapy. We suggested a possible network diagram based on the existing theory and the preliminary results of candidate miRNAs and their targets in HeLa cells during development of drug resistance.
Insights
MicroRNAs (miRNAs) play a crucial role in cervical cancer drug resistance. Specific miRNAs, like miR-182 and miR-15b, are altered in cisplatin-resistant cells, suggesting they could be therapeutic targets to improve chemotherapy effectiveness.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chemotherapy is a primary cancer treatment, but drug resistance, particularly in cervical cancer, limits long-term efficacy.
- Cisplatin is a widely used chemotherapy agent, and understanding resistance mechanisms is critical.
- MicroRNAs (miRNAs) are increasingly recognized for their roles in cancer development and drug resistance.
Purpose of the Study:
- To investigate the role of specific miRNAs in the development of cisplatin resistance in cervical cancer (HeLa) cells.
- To identify alterations in miRNA and target mRNA expression associated with acquired cisplatin resistance.
- To explore the potential of miRNAs as therapeutic targets for overcoming chemotherapy resistance in cervical cancer.
Main Methods:
- Generation and maintenance of four levels of cisplatin-resistant HeLa cell lines (HeLa/CR1-CR4).
- Selection of five candidate miRNAs (miR-183, miR-182, miR-30a, miR-15b, miR-16) and their target mRNAs based on prior research.
- Real-time RT-PCR was used to quantify the relative expression levels of selected miRNAs and their corresponding mRNAs.
Main Results:
- Upregulation of miR-182 and miR-15b, and significant downregulation of miR-30a were observed in cisplatin-resistant HeLa cell lines compared to the parent cells.
- The identified target mRNAs of these differentially expressed miRNAs are implicated in mechanisms of drug resistance.
- Altered expression patterns of these miRNAs in resistant cells suggest a link between specific miRNAs and acquired cisplatin resistance in cervical cancer.
Conclusions:
- Distinct miRNA expression profiles are associated with cisplatin resistance in HeLa cells.
- These findings indicate that specific miRNAs could serve as potential therapeutic targets to sensitize cervical cancer cells to chemotherapy.
- A preliminary network model of candidate miRNAs and their targets in drug-resistant HeLa cells was proposed.
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