miR-125b suppresses oral oncogenicity by targeting the anti-oxidative gene PRXL2A
Oral squamous cell carcinoma (OSCC) is a globally prevalent malignancy. The molecular mechanisms of this cancer are not well understood and acquire elucidation. Peroxiredoxin like 2A (PRXL2A) has been reported to be an antioxidant protein that protects cells from oxidative stress. Our previous study...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-04-01
|
| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231718309674 |
| _version_ | 1828762796633882624 |
|---|---|
| author | Yi-Fen Chen Yun-Yen Wei Cheng-Chieh Yang Chung-Ji Liu Li-Yin Yeh Chung-Hsien Chou Kuo-Wei Chang Shu-Chun Lin |
| author_facet | Yi-Fen Chen Yun-Yen Wei Cheng-Chieh Yang Chung-Ji Liu Li-Yin Yeh Chung-Hsien Chou Kuo-Wei Chang Shu-Chun Lin |
| author_sort | Yi-Fen Chen |
| collection | DOAJ |
| description | Oral squamous cell carcinoma (OSCC) is a globally prevalent malignancy. The molecular mechanisms of this cancer are not well understood and acquire elucidation. Peroxiredoxin like 2A (PRXL2A) has been reported to be an antioxidant protein that protects cells from oxidative stress. Our previous study identified an association between PRXL2A upregulation in OSCC and a worse patient prognosis. MicroRNAs (miRNAs) are small non-coding RNAs that are involved in the modulation of biological/pathological properties. The miR-125 family of genes drive pluripotent regulation across a wide variety of cancers. In this study, we identify the oncogenic eligibility of PRXL2A and clarify miR-125b as its upstream regulator. Downregulation of miR-125b can be observed in OSCC tumors. Lower miR-125b expression in tumors results in a worse patient prognosis at the relatively early stage. Reporter assays are able to validate that PRXL2A is a direct target of miR-125b. Exogenous miR-125b expression in OSCC cells results in increased oxidative stress, increased drug sensitivity, and suppressor activity that is paralleled by the knockout of PRXL2A gene. The suppressor activity of miR-125b is able to be rescued by PRXL2A, which suggests the existence of a miR-125b-PRXL2A regulatory axis that is part of OSCC pathogenesis. Nuclear factor-erythroid 2-related factor 2 (NRF2) was found to be a downstream effector of the miR-125b-PRXL2A cascade. As a whole, this study has pinpointed novel clues demonstrating that downregulation of miR-125b suppressor underlies upregulation of PRXL2A in OSCC, and this then protects the affected tumor cells from oxidative stress. Keywords: HNSCC, miR-125, NRF2, Oxidation, Peroxiredoxin like 2A |
| first_indexed | 2024-12-11T01:50:40Z |
| format | Article |
| id | doaj.art-7175bd6349be42ea873c69f319ce7983 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-11T01:50:40Z |
| publishDate | 2019-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-7175bd6349be42ea873c69f319ce79832022-12-22T01:24:46ZengElsevierRedox Biology2213-23172019-04-0122miR-125b suppresses oral oncogenicity by targeting the anti-oxidative gene PRXL2AYi-Fen Chen0Yun-Yen Wei1Cheng-Chieh Yang2Chung-Ji Liu3Li-Yin Yeh4Chung-Hsien Chou5Kuo-Wei Chang6Shu-Chun Lin7Institute of Oral Biology, National Yang-Ming University, Taipei, TaiwanInstitute of Oral Biology, National Yang-Ming University, Taipei, TaiwanInstitute of Oral Biology, National Yang-Ming University, Taipei, Taiwan; Department of Dentistry, National Yang-Ming University, Taipei, Taiwan; Department of Stomatology, Taipei Veterans General Hospital, Taipei, TaiwanDepartment of Dentistry, National Yang-Ming University, Taipei, Taiwan; Department of Dentistry, MacKay Memorial Hospital, Taipei, TaiwanInstitute of Oral Biology, National Yang-Ming University, Taipei, TaiwanInstitute of Oral Biology, National Yang-Ming University, Taipei, TaiwanInstitute of Oral Biology, National Yang-Ming University, Taipei, Taiwan; Department of Dentistry, National Yang-Ming University, Taipei, Taiwan; Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan; Corresponding author. Department of Dentistry, School of Dentistry, National Yang-Ming University, No. 155, Li-Nong St., Section 2, Taipei, 112, Taiwan. Tel.:+8862 28267223; fax: +8862 28264053.Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan; Department of Dentistry, National Yang-Ming University, Taipei, Taiwan; Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan; Corresponding author. Institute of Oral Biology, School of Dentistry, National Yang-Ming University, No. 155, Li-Nong St., Section 2, Taipei, 112, Taiwan. Tel.:+8862 28267272; fax: +8862 28264053.Oral squamous cell carcinoma (OSCC) is a globally prevalent malignancy. The molecular mechanisms of this cancer are not well understood and acquire elucidation. Peroxiredoxin like 2A (PRXL2A) has been reported to be an antioxidant protein that protects cells from oxidative stress. Our previous study identified an association between PRXL2A upregulation in OSCC and a worse patient prognosis. MicroRNAs (miRNAs) are small non-coding RNAs that are involved in the modulation of biological/pathological properties. The miR-125 family of genes drive pluripotent regulation across a wide variety of cancers. In this study, we identify the oncogenic eligibility of PRXL2A and clarify miR-125b as its upstream regulator. Downregulation of miR-125b can be observed in OSCC tumors. Lower miR-125b expression in tumors results in a worse patient prognosis at the relatively early stage. Reporter assays are able to validate that PRXL2A is a direct target of miR-125b. Exogenous miR-125b expression in OSCC cells results in increased oxidative stress, increased drug sensitivity, and suppressor activity that is paralleled by the knockout of PRXL2A gene. The suppressor activity of miR-125b is able to be rescued by PRXL2A, which suggests the existence of a miR-125b-PRXL2A regulatory axis that is part of OSCC pathogenesis. Nuclear factor-erythroid 2-related factor 2 (NRF2) was found to be a downstream effector of the miR-125b-PRXL2A cascade. As a whole, this study has pinpointed novel clues demonstrating that downregulation of miR-125b suppressor underlies upregulation of PRXL2A in OSCC, and this then protects the affected tumor cells from oxidative stress. Keywords: HNSCC, miR-125, NRF2, Oxidation, Peroxiredoxin like 2Ahttp://www.sciencedirect.com/science/article/pii/S2213231718309674 |
| spellingShingle | Yi-Fen Chen Yun-Yen Wei Cheng-Chieh Yang Chung-Ji Liu Li-Yin Yeh Chung-Hsien Chou Kuo-Wei Chang Shu-Chun Lin miR-125b suppresses oral oncogenicity by targeting the anti-oxidative gene PRXL2A Redox Biology |
| title | miR-125b suppresses oral oncogenicity by targeting the anti-oxidative gene PRXL2A |
| title_full | miR-125b suppresses oral oncogenicity by targeting the anti-oxidative gene PRXL2A |
| title_fullStr | miR-125b suppresses oral oncogenicity by targeting the anti-oxidative gene PRXL2A |
| title_full_unstemmed | miR-125b suppresses oral oncogenicity by targeting the anti-oxidative gene PRXL2A |
| title_short | miR-125b suppresses oral oncogenicity by targeting the anti-oxidative gene PRXL2A |
| title_sort | mir 125b suppresses oral oncogenicity by targeting the anti oxidative gene prxl2a |
| url | http://www.sciencedirect.com/science/article/pii/S2213231718309674 |
| work_keys_str_mv | AT yifenchen mir125bsuppressesoraloncogenicitybytargetingtheantioxidativegeneprxl2a AT yunyenwei mir125bsuppressesoraloncogenicitybytargetingtheantioxidativegeneprxl2a AT chengchiehyang mir125bsuppressesoraloncogenicitybytargetingtheantioxidativegeneprxl2a AT chungjiliu mir125bsuppressesoraloncogenicitybytargetingtheantioxidativegeneprxl2a AT liyinyeh mir125bsuppressesoraloncogenicitybytargetingtheantioxidativegeneprxl2a AT chunghsienchou mir125bsuppressesoraloncogenicitybytargetingtheantioxidativegeneprxl2a AT kuoweichang mir125bsuppressesoraloncogenicitybytargetingtheantioxidativegeneprxl2a AT shuchunlin mir125bsuppressesoraloncogenicitybytargetingtheantioxidativegeneprxl2a |