Long Non-Coding RNA Myosin Light Chain Kinase Antisense 1 Plays an Oncogenic Role in Gallbladder Carcinoma by Promoting Chemoresistance and Proliferation
Yongliang Li,1,* Mi Tian,2,* Dongqing Zhang,1 Yifei Zhuang,1 Zhimin Li,1 Shenqi Xie,1 Keyu Sun1 1Department of Emergency, Minhang Hospital, Fudan University, Shanghai, 200040, People’s Republic of China; 2Department of Intensive Care Unit, Huashan Hospital, Fudan University, Shanghai...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2021-08-01
|
| Series: | Cancer Management and Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/long-non-coding-rna-myosin-light-chain-kinase-antisense-1-plays-an-onc-peer-reviewed-fulltext-article-CMAR |
| _version_ | 1818607786397794304 |
|---|---|
| author | Li Y Tian M Zhang D Zhuang Y Li Z Xie S Sun K |
| author_facet | Li Y Tian M Zhang D Zhuang Y Li Z Xie S Sun K |
| author_sort | Li Y |
| collection | DOAJ |
| description | Yongliang Li,1,* Mi Tian,2,* Dongqing Zhang,1 Yifei Zhuang,1 Zhimin Li,1 Shenqi Xie,1 Keyu Sun1 1Department of Emergency, Minhang Hospital, Fudan University, Shanghai, 200040, People’s Republic of China; 2Department of Intensive Care Unit, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China*These authors contributed equally to this workCorrespondence: Keyu SunDepartment of Emergency, Minhang Hospital, Fudan University, Shanghai, 200040, People’s Republic of ChinaTel +86 18930536861Email hoceima@126.comBackground: Long non-coding RNAs (lncRNAs) have been reported to play critical roles in human tumours, including gallbladder carcinoma (GBC). However, their biological functions and molecular mechanisms in tumorigenesis and progression remain largely unknown.Methods: Quantitative polymerase chain reaction (qPCR) was used to verify the expression of lncRNA myosin light chain kinase antisense RNA 1 (MYLK-AS1) in 120 pairs of GBC tissues and paired adjacent non-tumour tissues, as well as in six different GBC cell lines (NOZ, EH-GB1, OCUG-1, GBC-SD, SGC-996 and QBC-939). Cell counting kit 8 was applied to explore cell proliferation and drug sensitivity assays. The target miRNAs (miR) of MYLK-AS1 and downstream target genes were predicted using Starbase 3.0 software and confirmed by double luciferase reporting test. The expression of proteins was assessed using Western blot assay.Results: Here, we demonstrated that MYLK-AS1 was significantly upregulated and correlated with a poor prognosis and poor clinical characteristics in GBC. Furthermore, the forced expression of MYLK-AS1 significantly promoted GBC cell proliferation and resistance to gemcitabine in vitro. Mechanistically, MYLK-AS1 functioned as an efficient miR-217 sponge, thereby releasing the inhibition of enhancer of zeste 2 polycomb repressive complex 2 (EZH2) subunit expression. MYLK-AS1 promoted GBC cell proliferation and resistance to gemcitabine by upregulating EZH2 expression, and EZH2 was confirmed as a direct target of miR-217.Discussion: Our results confirmed that the chemoresistant driver MYLK-AS1 might be a promising candidate as a therapeutic target for the treatment of advanced GBC.Keywords: chemoresistance, GBC, lncRNA, proliferation |
| first_indexed | 2024-12-16T14:32:17Z |
| format | Article |
| id | doaj.art-fb989c79271b4053bfacd89d5190f471 |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-16T14:32:17Z |
| publishDate | 2021-08-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-fb989c79271b4053bfacd89d5190f4712022-12-21T22:28:12ZengDove Medical PressCancer Management and Research1179-13222021-08-01Volume 136219623067635Long Non-Coding RNA Myosin Light Chain Kinase Antisense 1 Plays an Oncogenic Role in Gallbladder Carcinoma by Promoting Chemoresistance and ProliferationLi YTian MZhang DZhuang YLi ZXie SSun KYongliang Li,1,* Mi Tian,2,* Dongqing Zhang,1 Yifei Zhuang,1 Zhimin Li,1 Shenqi Xie,1 Keyu Sun1 1Department of Emergency, Minhang Hospital, Fudan University, Shanghai, 200040, People’s Republic of China; 2Department of Intensive Care Unit, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China*These authors contributed equally to this workCorrespondence: Keyu SunDepartment of Emergency, Minhang Hospital, Fudan University, Shanghai, 200040, People’s Republic of ChinaTel +86 18930536861Email hoceima@126.comBackground: Long non-coding RNAs (lncRNAs) have been reported to play critical roles in human tumours, including gallbladder carcinoma (GBC). However, their biological functions and molecular mechanisms in tumorigenesis and progression remain largely unknown.Methods: Quantitative polymerase chain reaction (qPCR) was used to verify the expression of lncRNA myosin light chain kinase antisense RNA 1 (MYLK-AS1) in 120 pairs of GBC tissues and paired adjacent non-tumour tissues, as well as in six different GBC cell lines (NOZ, EH-GB1, OCUG-1, GBC-SD, SGC-996 and QBC-939). Cell counting kit 8 was applied to explore cell proliferation and drug sensitivity assays. The target miRNAs (miR) of MYLK-AS1 and downstream target genes were predicted using Starbase 3.0 software and confirmed by double luciferase reporting test. The expression of proteins was assessed using Western blot assay.Results: Here, we demonstrated that MYLK-AS1 was significantly upregulated and correlated with a poor prognosis and poor clinical characteristics in GBC. Furthermore, the forced expression of MYLK-AS1 significantly promoted GBC cell proliferation and resistance to gemcitabine in vitro. Mechanistically, MYLK-AS1 functioned as an efficient miR-217 sponge, thereby releasing the inhibition of enhancer of zeste 2 polycomb repressive complex 2 (EZH2) subunit expression. MYLK-AS1 promoted GBC cell proliferation and resistance to gemcitabine by upregulating EZH2 expression, and EZH2 was confirmed as a direct target of miR-217.Discussion: Our results confirmed that the chemoresistant driver MYLK-AS1 might be a promising candidate as a therapeutic target for the treatment of advanced GBC.Keywords: chemoresistance, GBC, lncRNA, proliferationhttps://www.dovepress.com/long-non-coding-rna-myosin-light-chain-kinase-antisense-1-plays-an-onc-peer-reviewed-fulltext-article-CMARchemoresistancegbclncrnaproliferation |
| spellingShingle | Li Y Tian M Zhang D Zhuang Y Li Z Xie S Sun K Long Non-Coding RNA Myosin Light Chain Kinase Antisense 1 Plays an Oncogenic Role in Gallbladder Carcinoma by Promoting Chemoresistance and Proliferation Cancer Management and Research chemoresistance gbc lncrna proliferation |
| title | Long Non-Coding RNA Myosin Light Chain Kinase Antisense 1 Plays an Oncogenic Role in Gallbladder Carcinoma by Promoting Chemoresistance and Proliferation |
| title_full | Long Non-Coding RNA Myosin Light Chain Kinase Antisense 1 Plays an Oncogenic Role in Gallbladder Carcinoma by Promoting Chemoresistance and Proliferation |
| title_fullStr | Long Non-Coding RNA Myosin Light Chain Kinase Antisense 1 Plays an Oncogenic Role in Gallbladder Carcinoma by Promoting Chemoresistance and Proliferation |
| title_full_unstemmed | Long Non-Coding RNA Myosin Light Chain Kinase Antisense 1 Plays an Oncogenic Role in Gallbladder Carcinoma by Promoting Chemoresistance and Proliferation |
| title_short | Long Non-Coding RNA Myosin Light Chain Kinase Antisense 1 Plays an Oncogenic Role in Gallbladder Carcinoma by Promoting Chemoresistance and Proliferation |
| title_sort | long non coding rna myosin light chain kinase antisense 1 plays an oncogenic role in gallbladder carcinoma by promoting chemoresistance and proliferation |
| topic | chemoresistance gbc lncrna proliferation |
| url | https://www.dovepress.com/long-non-coding-rna-myosin-light-chain-kinase-antisense-1-plays-an-onc-peer-reviewed-fulltext-article-CMAR |
| work_keys_str_mv | AT liy longnoncodingrnamyosinlightchainkinaseantisense1playsanoncogenicroleingallbladdercarcinomabypromotingchemoresistanceandproliferation AT tianm longnoncodingrnamyosinlightchainkinaseantisense1playsanoncogenicroleingallbladdercarcinomabypromotingchemoresistanceandproliferation AT zhangd longnoncodingrnamyosinlightchainkinaseantisense1playsanoncogenicroleingallbladdercarcinomabypromotingchemoresistanceandproliferation AT zhuangy longnoncodingrnamyosinlightchainkinaseantisense1playsanoncogenicroleingallbladdercarcinomabypromotingchemoresistanceandproliferation AT liz longnoncodingrnamyosinlightchainkinaseantisense1playsanoncogenicroleingallbladdercarcinomabypromotingchemoresistanceandproliferation AT xies longnoncodingrnamyosinlightchainkinaseantisense1playsanoncogenicroleingallbladdercarcinomabypromotingchemoresistanceandproliferation AT sunk longnoncodingrnamyosinlightchainkinaseantisense1playsanoncogenicroleingallbladdercarcinomabypromotingchemoresistanceandproliferation |