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- Title
MicroRNA 29a therapy for CEACAM6-expressing lung adenocarcinoma.
- Authors
Son, Seung-Myoung; Yun, Jieun; Kim, Dong-Wook; Jung, Young-Suk; Han, Sang-Bae; Lee, Yong Hee; Han, Hye Sook; Woo, Chang Gok; Lee, Ho-Chang; Lee, Ok-Jun
- Abstract
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.
- Subjects
CELL adhesion molecules; PEPTIDE nucleic acids; CANCER cell growth; NON-small-cell lung carcinoma; TUMOR growth
- Publication
BMC Cancer, 2023, Vol 23, Issue 1, p1
- ISSN
1471-2407
- Publication type
Article
- DOI
10.1186/s12885-023-11352-w