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Updated: Jul 16, 2025
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MicroRNA 29a therapy for CEACAM6-expressing lung adenocarcinoma
Seung-Myoung Son1,2, Jieun Yun3, Dong-Wook Kim4
1Department of Pathology, Chungbuk National University Hospital, Cheongju, Republic of Korea.
Background:
Non-coding microRNAs (miRNAs) play critical roles in tumor progression and hold great promise as therapeutic agents for multiple cancers. MicroRNA 29a (miR-29a) is a tumor suppressor miRNA that inhibits cancer cell growth and tumor progression in non-small cell lung cancer. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), which plays an important role in lung cancer progression, has been identified as a target of miR-29a. Here, we evaluated the therapeutic efficacy of a peptide vector capable of delivering miR-29a intracellularly using the acidic tumor microenvironment in a lung adenocarcinoma xenograft mouse model.
Methods:
A miRNA delivery vector was constructed by tethering the peptide nucleic acid form of miR-29a to a peptide with a low pH-induced transmembrane structure (pHLIP) to enable transport of the miRNAs across the plasma membrane. Tumor suppressive effects of pHLIP-miR29a on lung adenocarcinoma development in vivo were assessed using a BALB/c xenograft model injected with A549 cells.
Results:
Incubation of A549 cells with pHLIP-miR-29a at an acidic pH downregulated endogenous CEACAM6 expression and reduced cell viability. Intravenous injection of the mice with pHLIP-miR-29a inhibited tumor growth by up to 18.1%. Intraperitoneal injection of cisplatin reduced tumor volume by 29.9%. Combined pHLIP-miR-29a + cisplatin treatment had an additive effect, reducing tumor volume up to 39.7%.
Conclusions:
Delivery of miR-29a to lung adenocarcinoma cells using a pHLIP-mediated method has therapeutic potential as a unique cancer treatment approach.
Insights
A novel peptide vector delivered microRNA 29a (miR-29a) to lung cancer cells, inhibiting tumor growth. This approach, combined with cisplatin, showed additive therapeutic effects in a mouse model.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Non-coding microRNAs (miRNAs) are crucial in cancer progression and potential therapeutics.
- MicroRNA 29a (miR-29a) acts as a tumor suppressor in non-small cell lung cancer.
- CEACAM6 is implicated in lung cancer progression and is a target of miR-29a.
Purpose of the Study:
- To evaluate the therapeutic efficacy of a peptide vector delivering miR-29a.
- To utilize the acidic tumor microenvironment for intracellular miRNA delivery.
- To assess the treatment in a lung adenocarcinoma xenograft mouse model.
Main Methods:
- Constructed a miRNA delivery vector by linking miR-29a to a pH-low insertion peptide (pHLIP).
- Assessed tumor suppressive effects of pHLIP-miR-29a in a BALB/c xenograft model using A549 lung adenocarcinoma cells.
- Evaluated effects on CEACAM6 expression, cell viability, and tumor growth in vivo.
Main Results:
- pHLIP-miR-29a downregulated CEACAM6 and reduced viability of A549 cells at acidic pH.
- Intravenous pHLIP-miR-29a inhibited tumor growth by 18.1%.
- Combined pHLIP-miR-29a and cisplatin treatment resulted in a 39.7% reduction in tumor volume.
Conclusions:
- pHLIP-mediated delivery of miR-29a shows therapeutic potential for lung adenocarcinoma.
- This approach offers a novel strategy for cancer treatment.
- Targeting CEACAM6 with miR-29a presents a promising avenue for lung cancer therapy.
