Circulating miR-320a Acts as a Tumor Suppressor and Prognostic Factor in Non-small Cell Lung Cancer
Dysregulated expression profiles of microRNAs (miRNAs) have been observed in several types of cancer, including non-small cell lung cancer (NSCLC); however, the diagnostic and prognostic potential of circulating miRNAs in NSCLC remains largely undefined. Here we found that circulating miR-320a was s...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.645475/full |
| _version_ | 1818722123783340032 |
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| author | Akanksha Khandelwal Uttam Sharma Tushar Singh Barwal Rajeev Kumar Seam Manish Gupta Manjit Kaur Rana Karen M. Vasquez Aklank Jain |
| author_facet | Akanksha Khandelwal Uttam Sharma Tushar Singh Barwal Rajeev Kumar Seam Manish Gupta Manjit Kaur Rana Karen M. Vasquez Aklank Jain |
| author_sort | Akanksha Khandelwal |
| collection | DOAJ |
| description | Dysregulated expression profiles of microRNAs (miRNAs) have been observed in several types of cancer, including non-small cell lung cancer (NSCLC); however, the diagnostic and prognostic potential of circulating miRNAs in NSCLC remains largely undefined. Here we found that circulating miR-320a was significantly down-regulated (~5.87-fold; p < 0.0001) in NSCLC patients (n = 80) compared to matched control plasma samples from healthy subjects (n = 80). Kaplan-Meier survival analysis revealed that NSCLC patients with lower levels of circulating miR-320a had overall poorer prognosis and survival rates compared to patients with higher levels (p < 0.0001). Moreover, the diagnostic and prognostic potential of miR-320a correlated with clinicopathological characteristics such as tumor size, tumor node metastasis (TNM) stage, and lymph node metastasis. Functionally, depletion of miR-320a in human A549 lung adenocarcinoma cells induced their metastatic potential and reduced apoptosis, which was reversed by exogenous re-expression of miR-320a mimics, indicating that miR-320a has a tumor-suppressive role in NSCLC. These results were further supported by high levels of epithelial-mesenchymal transition (EMT) marker proteins (e.g., Beta-catenin, MMP9, and E-cadherin) in lung cancer cells and tissues via immunoblot and immunohistochemistry experiments. Moreover, through bioinformatics and dual-luciferase reporter assays, we demonstrated that AKT3 was a direct target of miR-320a. In addition, AKT3-associated PI3K/AKT/mTOR protein-signaling pathways were elevated with down-regulated miR-320a levels in NSCLC. These composite data indicate that circulating miR-320a may function as a tumor-suppressor miRNA with potential as a prognostic marker for NSCLC patients. |
| first_indexed | 2024-12-17T20:49:38Z |
| format | Article |
| id | doaj.art-b351b5904f03464286f6542ad2886f1e |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-17T20:49:38Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-b351b5904f03464286f6542ad2886f1e2022-12-21T21:33:04ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-03-011110.3389/fonc.2021.645475645475Circulating miR-320a Acts as a Tumor Suppressor and Prognostic Factor in Non-small Cell Lung CancerAkanksha Khandelwal0Uttam Sharma1Tushar Singh Barwal2Rajeev Kumar Seam3Manish Gupta4Manjit Kaur Rana5Karen M. Vasquez6Aklank Jain7Department of Biochemistry and Microbial Sciences, Central University of Punjab, Bathinda, IndiaDepartment of Zoology, Central University of Punjab, Bathinda, IndiaDepartment of Zoology, Central University of Punjab, Bathinda, IndiaDepartment of Radiation Oncology, Indira Gandhi Medical College, Shimla, IndiaDepartment of Radiation Oncology, Indira Gandhi Medical College, Shimla, IndiaLab Medicine, Department of Pathology, All India Institute of Medical Sciences, Bathinda, IndiaDivision of Pharmacology and Toxicology, College of Pharmacy, Dell Pediatric Research Institute, The University of Texas at Austin, Austin, TX, United StatesDepartment of Zoology, Central University of Punjab, Bathinda, IndiaDysregulated expression profiles of microRNAs (miRNAs) have been observed in several types of cancer, including non-small cell lung cancer (NSCLC); however, the diagnostic and prognostic potential of circulating miRNAs in NSCLC remains largely undefined. Here we found that circulating miR-320a was significantly down-regulated (~5.87-fold; p < 0.0001) in NSCLC patients (n = 80) compared to matched control plasma samples from healthy subjects (n = 80). Kaplan-Meier survival analysis revealed that NSCLC patients with lower levels of circulating miR-320a had overall poorer prognosis and survival rates compared to patients with higher levels (p < 0.0001). Moreover, the diagnostic and prognostic potential of miR-320a correlated with clinicopathological characteristics such as tumor size, tumor node metastasis (TNM) stage, and lymph node metastasis. Functionally, depletion of miR-320a in human A549 lung adenocarcinoma cells induced their metastatic potential and reduced apoptosis, which was reversed by exogenous re-expression of miR-320a mimics, indicating that miR-320a has a tumor-suppressive role in NSCLC. These results were further supported by high levels of epithelial-mesenchymal transition (EMT) marker proteins (e.g., Beta-catenin, MMP9, and E-cadherin) in lung cancer cells and tissues via immunoblot and immunohistochemistry experiments. Moreover, through bioinformatics and dual-luciferase reporter assays, we demonstrated that AKT3 was a direct target of miR-320a. In addition, AKT3-associated PI3K/AKT/mTOR protein-signaling pathways were elevated with down-regulated miR-320a levels in NSCLC. These composite data indicate that circulating miR-320a may function as a tumor-suppressor miRNA with potential as a prognostic marker for NSCLC patients.https://www.frontiersin.org/articles/10.3389/fonc.2021.645475/fullmiR-320aNSCLCliquid biopsycancerprognosis |
| spellingShingle | Akanksha Khandelwal Uttam Sharma Tushar Singh Barwal Rajeev Kumar Seam Manish Gupta Manjit Kaur Rana Karen M. Vasquez Aklank Jain Circulating miR-320a Acts as a Tumor Suppressor and Prognostic Factor in Non-small Cell Lung Cancer Frontiers in Oncology miR-320a NSCLC liquid biopsy cancer prognosis |
| title | Circulating miR-320a Acts as a Tumor Suppressor and Prognostic Factor in Non-small Cell Lung Cancer |
| title_full | Circulating miR-320a Acts as a Tumor Suppressor and Prognostic Factor in Non-small Cell Lung Cancer |
| title_fullStr | Circulating miR-320a Acts as a Tumor Suppressor and Prognostic Factor in Non-small Cell Lung Cancer |
| title_full_unstemmed | Circulating miR-320a Acts as a Tumor Suppressor and Prognostic Factor in Non-small Cell Lung Cancer |
| title_short | Circulating miR-320a Acts as a Tumor Suppressor and Prognostic Factor in Non-small Cell Lung Cancer |
| title_sort | circulating mir 320a acts as a tumor suppressor and prognostic factor in non small cell lung cancer |
| topic | miR-320a NSCLC liquid biopsy cancer prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.645475/full |
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