Unlocking melanoma Suppression: Insights from Plasma-Induced potent miRNAs through PI3K-AKT-ZEB1 axis
Introduction: Melanoma is a rare but highly malignant form of skin cancer. Although recent targeted and immune-based therapies have improved survival rates by 10–15%, effective melanoma treatment remains challenging. Therefore, novel, combinatorial therapy options such as non-thermal atmospheric pre...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | Journal of Advanced Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123224000845 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832595778393079808 |
|---|---|
| author | Pradeep Bhartiya Apurva Jaiswal Manorma Negi Neha Kaushik Eun Ha Choi Nagendra Kumar Kaushik |
| author_facet | Pradeep Bhartiya Apurva Jaiswal Manorma Negi Neha Kaushik Eun Ha Choi Nagendra Kumar Kaushik |
| author_sort | Pradeep Bhartiya |
| collection | DOAJ |
| description | Introduction: Melanoma is a rare but highly malignant form of skin cancer. Although recent targeted and immune-based therapies have improved survival rates by 10–15%, effective melanoma treatment remains challenging. Therefore, novel, combinatorial therapy options such as non-thermal atmospheric pressure plasma (NTP) are being investigated to inhibit and prevent chemoresistance. Although several studies have reported the apoptotic and inhibitory effects of reactive oxygen species produced by NTP in the context of melanoma, the intricate molecular network that determines the role of microRNAs (miRNAs) in regulating NTP-mediated cell death remains unexplored. Objectives: This study aimed to explore the molecular mechanisms and miRNA networks regulated by NTP-induced oxidative stress in melanoma cells. Methods: Melanoma cells were exposed to NTP and then subjected to high-throughput miRNA sequencing to identify NTP-regulated miRNAs. Various biological processes and underlying molecular mechanisms were assessed using Alamar Blue, propidium iodide (PI) uptake, cell migration, and clonogenic assays followed by qRT-PCR and flow cytometry. Results: NTP exposure for 3 min was sufficient to modulate the expression of several miRNAs, inhibiting cell growth. Persistent NTP exposure for 5 min increased differential miRNA regulation, PI uptake, and the expression of genes involved in cell cycle arrest and death. qPCR confirmed that miR-200b-3p and miR-215-5p upregulation contributed to decreased cell viability and migration. Mechanistically, inhibiting miR-200b-3p and miR-215-5p in SK-2 cells enhanced ZEB1, PI3K, and AKT expression, increasing cell proliferation and viability. Conclusion: This study demonstrated that NTP exposure for 5 min results in the differential regulation of miRNAs related to the PI3K-AKT-ZEB1 axis and cell cycle dysregulation to facilitate melanoma suppression. |
| format | Article |
| id | doaj-art-8e897576dc9f4fd6a6eecb7a1c2d8c5c |
| institution | Kabale University |
| issn | 2090-1232 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Advanced Research |
| spelling | doaj-art-8e897576dc9f4fd6a6eecb7a1c2d8c5c2025-01-18T05:04:21ZengElsevierJournal of Advanced Research2090-12322025-02-0168147161Unlocking melanoma Suppression: Insights from Plasma-Induced potent miRNAs through PI3K-AKT-ZEB1 axisPradeep Bhartiya0Apurva Jaiswal1Manorma Negi2Neha Kaushik3Eun Ha Choi4Nagendra Kumar Kaushik5Plasma Bioscience Research Center, Department of Electrical and Biological Physics, Kwangwoon University, Seoul 01897, Republic of Korea; Department of Biotechnology, College of Engineering, The University of Suwon, Hwaseong 18323, Republic of KoreaPlasma Bioscience Research Center, Department of Electrical and Biological Physics, Kwangwoon University, Seoul 01897, Republic of KoreaPlasma Bioscience Research Center, Department of Electrical and Biological Physics, Kwangwoon University, Seoul 01897, Republic of KoreaDepartment of Biotechnology, College of Engineering, The University of Suwon, Hwaseong 18323, Republic of Korea; Corresponding authors.Plasma Bioscience Research Center, Department of Electrical and Biological Physics, Kwangwoon University, Seoul 01897, Republic of Korea; Corresponding authors.Plasma Bioscience Research Center, Department of Electrical and Biological Physics, Kwangwoon University, Seoul 01897, Republic of Korea; Corresponding authors.Introduction: Melanoma is a rare but highly malignant form of skin cancer. Although recent targeted and immune-based therapies have improved survival rates by 10–15%, effective melanoma treatment remains challenging. Therefore, novel, combinatorial therapy options such as non-thermal atmospheric pressure plasma (NTP) are being investigated to inhibit and prevent chemoresistance. Although several studies have reported the apoptotic and inhibitory effects of reactive oxygen species produced by NTP in the context of melanoma, the intricate molecular network that determines the role of microRNAs (miRNAs) in regulating NTP-mediated cell death remains unexplored. Objectives: This study aimed to explore the molecular mechanisms and miRNA networks regulated by NTP-induced oxidative stress in melanoma cells. Methods: Melanoma cells were exposed to NTP and then subjected to high-throughput miRNA sequencing to identify NTP-regulated miRNAs. Various biological processes and underlying molecular mechanisms were assessed using Alamar Blue, propidium iodide (PI) uptake, cell migration, and clonogenic assays followed by qRT-PCR and flow cytometry. Results: NTP exposure for 3 min was sufficient to modulate the expression of several miRNAs, inhibiting cell growth. Persistent NTP exposure for 5 min increased differential miRNA regulation, PI uptake, and the expression of genes involved in cell cycle arrest and death. qPCR confirmed that miR-200b-3p and miR-215-5p upregulation contributed to decreased cell viability and migration. Mechanistically, inhibiting miR-200b-3p and miR-215-5p in SK-2 cells enhanced ZEB1, PI3K, and AKT expression, increasing cell proliferation and viability. Conclusion: This study demonstrated that NTP exposure for 5 min results in the differential regulation of miRNAs related to the PI3K-AKT-ZEB1 axis and cell cycle dysregulation to facilitate melanoma suppression.http://www.sciencedirect.com/science/article/pii/S2090123224000845Non-thermal plasmamiRNA sequencingDifferential regulationMelanoma inhibition |
| spellingShingle | Pradeep Bhartiya Apurva Jaiswal Manorma Negi Neha Kaushik Eun Ha Choi Nagendra Kumar Kaushik Unlocking melanoma Suppression: Insights from Plasma-Induced potent miRNAs through PI3K-AKT-ZEB1 axis Journal of Advanced Research Non-thermal plasma miRNA sequencing Differential regulation Melanoma inhibition |
| title | Unlocking melanoma Suppression: Insights from Plasma-Induced potent miRNAs through PI3K-AKT-ZEB1 axis |
| title_full | Unlocking melanoma Suppression: Insights from Plasma-Induced potent miRNAs through PI3K-AKT-ZEB1 axis |
| title_fullStr | Unlocking melanoma Suppression: Insights from Plasma-Induced potent miRNAs through PI3K-AKT-ZEB1 axis |
| title_full_unstemmed | Unlocking melanoma Suppression: Insights from Plasma-Induced potent miRNAs through PI3K-AKT-ZEB1 axis |
| title_short | Unlocking melanoma Suppression: Insights from Plasma-Induced potent miRNAs through PI3K-AKT-ZEB1 axis |
| title_sort | unlocking melanoma suppression insights from plasma induced potent mirnas through pi3k akt zeb1 axis |
| topic | Non-thermal plasma miRNA sequencing Differential regulation Melanoma inhibition |
| url | http://www.sciencedirect.com/science/article/pii/S2090123224000845 |
| work_keys_str_mv | AT pradeepbhartiya unlockingmelanomasuppressioninsightsfromplasmainducedpotentmirnasthroughpi3kaktzeb1axis AT apurvajaiswal unlockingmelanomasuppressioninsightsfromplasmainducedpotentmirnasthroughpi3kaktzeb1axis AT manormanegi unlockingmelanomasuppressioninsightsfromplasmainducedpotentmirnasthroughpi3kaktzeb1axis AT nehakaushik unlockingmelanomasuppressioninsightsfromplasmainducedpotentmirnasthroughpi3kaktzeb1axis AT eunhachoi unlockingmelanomasuppressioninsightsfromplasmainducedpotentmirnasthroughpi3kaktzeb1axis AT nagendrakumarkaushik unlockingmelanomasuppressioninsightsfromplasmainducedpotentmirnasthroughpi3kaktzeb1axis |