Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis
Abstract The prevention and treatment of postmenopausal osteoporosis (PMOP) is a significant public health issue, and non-coding RNAs are of vital importance in this process. In this study, we find that the long non-coding RNA potassium voltage-gated channel subfamily Q member 1 overlapping transcri...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-02-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-29546-4 |
| _version_ | 1811165985892204544 |
|---|---|
| author | Ziyu Wang Hengshuo Zhang Qinghui Li Lu Zhang Lu Chen Hongliang Wang Yunzhen Chen |
| author_facet | Ziyu Wang Hengshuo Zhang Qinghui Li Lu Zhang Lu Chen Hongliang Wang Yunzhen Chen |
| author_sort | Ziyu Wang |
| collection | DOAJ |
| description | Abstract The prevention and treatment of postmenopausal osteoporosis (PMOP) is a significant public health issue, and non-coding RNAs are of vital importance in this process. In this study, we find that the long non-coding RNA potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (lncRNA KCNQ1OT1) can alleviate the ovariectomy-induced (OVX) PMOP in vivo. We determined that over-expression of KCNQ1OT1 could enhance functions of MC3T3-E1 cells, whereas an opposite trend was observed when KCNQ1OT1 was knocked down. Subsequently, miR-421-3p targeting KCNQ1OT1 was detected through a database search, and RNA fluorescent in situ hybridization, RNA immunoprecipitation, dual luciferase reporter assays all verified this relationship. Notably, KCNQ1OT1 stifled the miR-421-3p expression. The inhibition of proliferation, migration, and osteogenic differentiation caused by KCNQ1OT1 knock-down were reversed by an miR-421-3p inhibitor, further confirming the above findings. We verified that miR-421-3p specifically targeted the mammalian target of rapamycin (mTOR), and miR-421-3p inhibitor could reverse the negative effects of small interfering RNA of mTOR (si-mTOR) on MC3T3-E1 cells. Finally, osteoblasts isolated and cultured from OVX mice model and control mice also confirmed the observed trend. In combination, results mentioned above reveal that KCNQ1OT1 regulates MC3T3-E1 cell functions by regulating the miR-421-3p/mTOR axis. |
| first_indexed | 2024-04-10T15:45:03Z |
| format | Article |
| id | doaj.art-274d7202949d442ab1e4aeed31a38dc8 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-10T15:45:03Z |
| publishDate | 2023-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-274d7202949d442ab1e4aeed31a38dc82023-02-12T12:08:51ZengNature PortfolioScientific Reports2045-23222023-02-0113111710.1038/s41598-023-29546-4Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axisZiyu Wang0Hengshuo Zhang1Qinghui Li2Lu Zhang3Lu Chen4Hongliang Wang5Yunzhen Chen6Department of Orthopedics, Qilu Hospital of Shandong UniversityDepartment of Orthopedics, Qilu Hospital of Shandong UniversityDepartment of Orthopedics, Qilu Hospital of Shandong UniversityDepartment of Orthopedics, Qilu Hospital of Shandong UniversityCheeloo College of Medicine, Shandong UniversityDepartment of Orthopedics, Qilu Hospital of Shandong UniversityDepartment of Orthopedics, Qilu Hospital of Shandong UniversityAbstract The prevention and treatment of postmenopausal osteoporosis (PMOP) is a significant public health issue, and non-coding RNAs are of vital importance in this process. In this study, we find that the long non-coding RNA potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (lncRNA KCNQ1OT1) can alleviate the ovariectomy-induced (OVX) PMOP in vivo. We determined that over-expression of KCNQ1OT1 could enhance functions of MC3T3-E1 cells, whereas an opposite trend was observed when KCNQ1OT1 was knocked down. Subsequently, miR-421-3p targeting KCNQ1OT1 was detected through a database search, and RNA fluorescent in situ hybridization, RNA immunoprecipitation, dual luciferase reporter assays all verified this relationship. Notably, KCNQ1OT1 stifled the miR-421-3p expression. The inhibition of proliferation, migration, and osteogenic differentiation caused by KCNQ1OT1 knock-down were reversed by an miR-421-3p inhibitor, further confirming the above findings. We verified that miR-421-3p specifically targeted the mammalian target of rapamycin (mTOR), and miR-421-3p inhibitor could reverse the negative effects of small interfering RNA of mTOR (si-mTOR) on MC3T3-E1 cells. Finally, osteoblasts isolated and cultured from OVX mice model and control mice also confirmed the observed trend. In combination, results mentioned above reveal that KCNQ1OT1 regulates MC3T3-E1 cell functions by regulating the miR-421-3p/mTOR axis.https://doi.org/10.1038/s41598-023-29546-4 |
| spellingShingle | Ziyu Wang Hengshuo Zhang Qinghui Li Lu Zhang Lu Chen Hongliang Wang Yunzhen Chen Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis Scientific Reports |
| title | Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis |
| title_full | Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis |
| title_fullStr | Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis |
| title_full_unstemmed | Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis |
| title_short | Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis |
| title_sort | long non coding rna kcnq1ot1 alleviates postmenopausal osteoporosis by modulating mir 421 3p mtor axis |
| url | https://doi.org/10.1038/s41598-023-29546-4 |
| work_keys_str_mv | AT ziyuwang longnoncodingrnakcnq1ot1alleviatespostmenopausalosteoporosisbymodulatingmir4213pmtoraxis AT hengshuozhang longnoncodingrnakcnq1ot1alleviatespostmenopausalosteoporosisbymodulatingmir4213pmtoraxis AT qinghuili longnoncodingrnakcnq1ot1alleviatespostmenopausalosteoporosisbymodulatingmir4213pmtoraxis AT luzhang longnoncodingrnakcnq1ot1alleviatespostmenopausalosteoporosisbymodulatingmir4213pmtoraxis AT luchen longnoncodingrnakcnq1ot1alleviatespostmenopausalosteoporosisbymodulatingmir4213pmtoraxis AT hongliangwang longnoncodingrnakcnq1ot1alleviatespostmenopausalosteoporosisbymodulatingmir4213pmtoraxis AT yunzhenchen longnoncodingrnakcnq1ot1alleviatespostmenopausalosteoporosisbymodulatingmir4213pmtoraxis |