Inhibition of LINC00958 hinders the progression of osteoarthritis through regulation of the miR-214-3p/FOXM1 axis
Abstract Objective We investigated the impact of the long noncoding RNA LINC00958 on cellular activity and oxidative stress in osteoarthritis (OA). Methods We performed bioinformatics analysis via StarBase and luciferase reporter assays to predict and validate the interactions between LINC00958 and...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-01-01
|
| Series: | Journal of Orthopaedic Surgery and Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13018-024-04545-x |
| _version_ | 1827382052485332992 |
|---|---|
| author | Yingchuan Yin Qiaojuan He Jing He Ying Feng Yunyun Xu |
| author_facet | Yingchuan Yin Qiaojuan He Jing He Ying Feng Yunyun Xu |
| author_sort | Yingchuan Yin |
| collection | DOAJ |
| description | Abstract Objective We investigated the impact of the long noncoding RNA LINC00958 on cellular activity and oxidative stress in osteoarthritis (OA). Methods We performed bioinformatics analysis via StarBase and luciferase reporter assays to predict and validate the interactions between LINC00958 and miR-214-3p and between miR-214-3p and FOXM1. The expression levels of LINC00958, miR-214-3p, and FOXM1 were measured by qRT-PCR and western blotting. To assess effects on CHON-001 cells, we performed MTT proliferation assays, evaluated cytotoxicity with a lactate dehydrogenase (LDH) assay, and examined apoptosis through flow cytometry. Additionally, we measured the levels of apoptosis-related proteins, including BAX and BCL2, using western blotting. The secretion of inflammatory cytokines (IL-6, IL-8, and TNF-α) was measured using ELISA. Results Our findings confirmed that LINC00958 is a direct target of miR-214-3p. LINC00958 expression was upregulated but miR-214-3p expression was downregulated in both OA cells and IL-1β-stimulated CHON-001 cells compared to the corresponding control cells. Remarkably, miR-214-3p expression was further reduced after miR-214-3p inhibitor treatment but increased following LINC00958-siRNA stimulation. Silencing LINC00958 significantly decreased its expression, and this effect was reversed by miR-214-3p inhibitor treatment. Notably, LINC00958-siRNA transfection alleviated the IL-1β-induced inflammatory response, as evidenced by the increased cell viability, reduced LDH release, suppression of apoptosis, downregulated BAX expression, and elevated BCL2 levels. Moreover, LINC00958 silencing led to reduced secretion of inflammatory factors from IL-1β-stimulated CHON-001 cells. The opposite results were observed in the miR-214-3p inhibitor-transfected groups. Furthermore, in CHON-001 cells, miR-214-3p directly targeted FOXM1 and negatively regulated its expression. Conclusion Our findings suggest that downregulating LINC00958 mitigates IL-1β-induced injury in CHON-001 cells through the miR-214-3p/FOXM1 axis. These results imply that LINC00958 plays a role in OA development and may be a valuable therapeutic target for OA. |
| first_indexed | 2024-03-08T14:13:56Z |
| format | Article |
| id | doaj.art-310a86206b2b4b2288bbd35e5743b694 |
| institution | Directory Open Access Journal |
| issn | 1749-799X |
| language | English |
| last_indexed | 2024-03-08T14:13:56Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj.art-310a86206b2b4b2288bbd35e5743b6942024-01-14T12:30:10ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2024-01-0119111110.1186/s13018-024-04545-xInhibition of LINC00958 hinders the progression of osteoarthritis through regulation of the miR-214-3p/FOXM1 axisYingchuan Yin0Qiaojuan He1Jing He2Ying Feng3Yunyun Xu4Endocrinology Department, The Third People’s Hospital of HefeiEndocrinology Department, The Third People’s Hospital of HefeiEndocrinology Department, The Third People’s Hospital of HefeiEndocrinology Department, The Third People’s Hospital of HefeiEndocrinology Department, The Third People’s Hospital of HefeiAbstract Objective We investigated the impact of the long noncoding RNA LINC00958 on cellular activity and oxidative stress in osteoarthritis (OA). Methods We performed bioinformatics analysis via StarBase and luciferase reporter assays to predict and validate the interactions between LINC00958 and miR-214-3p and between miR-214-3p and FOXM1. The expression levels of LINC00958, miR-214-3p, and FOXM1 were measured by qRT-PCR and western blotting. To assess effects on CHON-001 cells, we performed MTT proliferation assays, evaluated cytotoxicity with a lactate dehydrogenase (LDH) assay, and examined apoptosis through flow cytometry. Additionally, we measured the levels of apoptosis-related proteins, including BAX and BCL2, using western blotting. The secretion of inflammatory cytokines (IL-6, IL-8, and TNF-α) was measured using ELISA. Results Our findings confirmed that LINC00958 is a direct target of miR-214-3p. LINC00958 expression was upregulated but miR-214-3p expression was downregulated in both OA cells and IL-1β-stimulated CHON-001 cells compared to the corresponding control cells. Remarkably, miR-214-3p expression was further reduced after miR-214-3p inhibitor treatment but increased following LINC00958-siRNA stimulation. Silencing LINC00958 significantly decreased its expression, and this effect was reversed by miR-214-3p inhibitor treatment. Notably, LINC00958-siRNA transfection alleviated the IL-1β-induced inflammatory response, as evidenced by the increased cell viability, reduced LDH release, suppression of apoptosis, downregulated BAX expression, and elevated BCL2 levels. Moreover, LINC00958 silencing led to reduced secretion of inflammatory factors from IL-1β-stimulated CHON-001 cells. The opposite results were observed in the miR-214-3p inhibitor-transfected groups. Furthermore, in CHON-001 cells, miR-214-3p directly targeted FOXM1 and negatively regulated its expression. Conclusion Our findings suggest that downregulating LINC00958 mitigates IL-1β-induced injury in CHON-001 cells through the miR-214-3p/FOXM1 axis. These results imply that LINC00958 plays a role in OA development and may be a valuable therapeutic target for OA.https://doi.org/10.1186/s13018-024-04545-xLINC00958OsteoarthritisInflammationmiR-214-3p/FOXM1 axis |
| spellingShingle | Yingchuan Yin Qiaojuan He Jing He Ying Feng Yunyun Xu Inhibition of LINC00958 hinders the progression of osteoarthritis through regulation of the miR-214-3p/FOXM1 axis Journal of Orthopaedic Surgery and Research LINC00958 Osteoarthritis Inflammation miR-214-3p/FOXM1 axis |
| title | Inhibition of LINC00958 hinders the progression of osteoarthritis through regulation of the miR-214-3p/FOXM1 axis |
| title_full | Inhibition of LINC00958 hinders the progression of osteoarthritis through regulation of the miR-214-3p/FOXM1 axis |
| title_fullStr | Inhibition of LINC00958 hinders the progression of osteoarthritis through regulation of the miR-214-3p/FOXM1 axis |
| title_full_unstemmed | Inhibition of LINC00958 hinders the progression of osteoarthritis through regulation of the miR-214-3p/FOXM1 axis |
| title_short | Inhibition of LINC00958 hinders the progression of osteoarthritis through regulation of the miR-214-3p/FOXM1 axis |
| title_sort | inhibition of linc00958 hinders the progression of osteoarthritis through regulation of the mir 214 3p foxm1 axis |
| topic | LINC00958 Osteoarthritis Inflammation miR-214-3p/FOXM1 axis |
| url | https://doi.org/10.1186/s13018-024-04545-x |
| work_keys_str_mv | AT yingchuanyin inhibitionoflinc00958hinderstheprogressionofosteoarthritisthroughregulationofthemir2143pfoxm1axis AT qiaojuanhe inhibitionoflinc00958hinderstheprogressionofosteoarthritisthroughregulationofthemir2143pfoxm1axis AT jinghe inhibitionoflinc00958hinderstheprogressionofosteoarthritisthroughregulationofthemir2143pfoxm1axis AT yingfeng inhibitionoflinc00958hinderstheprogressionofosteoarthritisthroughregulationofthemir2143pfoxm1axis AT yunyunxu inhibitionoflinc00958hinderstheprogressionofosteoarthritisthroughregulationofthemir2143pfoxm1axis |