Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a
Abstract Background Long noncoding RNA HULC is highly up-regulation in human hepatocellular carcinoma (HCC). However, the functions of HULC in hepatocarcinogenesis remains unclear. Methods RT-PCR, Western blotting, Chromatin immunoprecipitation (CHIP) assay, RNA Immunoprecipitation (RIP) and tumorig...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-06-01
|
| Series: | Molecular Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12943-018-0843-8 |
| _version_ | 1828814527797395456 |
|---|---|
| author | Xiaoru Xin Mengying Wu Qiuyu Meng Chen Wang Yanan Lu Yuxin Yang Xiaonan Li Qidi Zheng Hu Pu Xin Gui Tianming Li Jiao Li Song Jia Dongdong Lu |
| author_facet | Xiaoru Xin Mengying Wu Qiuyu Meng Chen Wang Yanan Lu Yuxin Yang Xiaonan Li Qidi Zheng Hu Pu Xin Gui Tianming Li Jiao Li Song Jia Dongdong Lu |
| author_sort | Xiaoru Xin |
| collection | DOAJ |
| description | Abstract Background Long noncoding RNA HULC is highly up-regulation in human hepatocellular carcinoma (HCC). However, the functions of HULC in hepatocarcinogenesis remains unclear. Methods RT-PCR, Western blotting, Chromatin immunoprecipitation (CHIP) assay, RNA Immunoprecipitation (RIP) and tumorignesis test in vitro and in vivo were performed. Results HULC is negatively associated with expression of PTEN or miR15a in patients of human liver cancer. Moreover, HULC accelerates malignant progression of liver cancer cells in vitro and in vivo. Mechanistically, HULC increasesthe expression of P62 via decreasing mature miR15a. On the other hand, excessive HULC increases the expression of LC3 on the level of transcription and then activates LC3 through Sirt1 (a deacetylase). Notably, HULC enhanced the interplay between LC3 and ATG3. Furthermore, HULC also increases the expression of becline-1(autophagy related gene). Therefore, HULC increases the cellular autophagy by increasing LC3II dependent on Sirt1.Noteworthy, excessive HULC reduces the expression of PTEN, β-catenin and enhances the expression of SAPK/JUNK, PKM2, CDK2, NOTCH1, C-Jun in liver cancer cells. Of significance, our observations also revealed that HULC inhibited PTEN through ubiquitin–proteasome system mediated by autophagy-P62.Ultimately,HULC activates AKT-PI3K-mTOR pathway through inhibiting PTEN in human liver cancer cells. Conclusions This study elucidates a novel mechanism that lncRNA HULC produces a vital function during hepatocarcinogenesis. |
| first_indexed | 2024-12-12T10:24:41Z |
| format | Article |
| id | doaj.art-e79c6c36839a4b0eb72b4c4e3638143a |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-12-12T10:24:41Z |
| publishDate | 2018-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-e79c6c36839a4b0eb72b4c4e3638143a2022-12-22T00:27:28ZengBMCMolecular Cancer1476-45982018-06-0117111610.1186/s12943-018-0843-8Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15aXiaoru Xin0Mengying Wu1Qiuyu Meng2Chen Wang3Yanan Lu4Yuxin Yang5Xiaonan Li6Qidi Zheng7Hu Pu8Xin Gui9Tianming Li10Jiao Li11Song Jia12Dongdong Lu13Research Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji UniversityResearch Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji UniversityResearch Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji UniversityResearch Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji UniversityResearch Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji UniversityResearch Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji UniversityResearch Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji UniversityResearch Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji UniversityResearch Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji UniversityResearch Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji UniversityResearch Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji UniversitySchool of Medicine, Tongji UniversitySchool of Medicine, Tongji UniversityResearch Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji UniversityAbstract Background Long noncoding RNA HULC is highly up-regulation in human hepatocellular carcinoma (HCC). However, the functions of HULC in hepatocarcinogenesis remains unclear. Methods RT-PCR, Western blotting, Chromatin immunoprecipitation (CHIP) assay, RNA Immunoprecipitation (RIP) and tumorignesis test in vitro and in vivo were performed. Results HULC is negatively associated with expression of PTEN or miR15a in patients of human liver cancer. Moreover, HULC accelerates malignant progression of liver cancer cells in vitro and in vivo. Mechanistically, HULC increasesthe expression of P62 via decreasing mature miR15a. On the other hand, excessive HULC increases the expression of LC3 on the level of transcription and then activates LC3 through Sirt1 (a deacetylase). Notably, HULC enhanced the interplay between LC3 and ATG3. Furthermore, HULC also increases the expression of becline-1(autophagy related gene). Therefore, HULC increases the cellular autophagy by increasing LC3II dependent on Sirt1.Noteworthy, excessive HULC reduces the expression of PTEN, β-catenin and enhances the expression of SAPK/JUNK, PKM2, CDK2, NOTCH1, C-Jun in liver cancer cells. Of significance, our observations also revealed that HULC inhibited PTEN through ubiquitin–proteasome system mediated by autophagy-P62.Ultimately,HULC activates AKT-PI3K-mTOR pathway through inhibiting PTEN in human liver cancer cells. Conclusions This study elucidates a novel mechanism that lncRNA HULC produces a vital function during hepatocarcinogenesis.http://link.springer.com/article/10.1186/s12943-018-0843-8Lnc RNA HULCPTENAutophagymiR15a |
| spellingShingle | Xiaoru Xin Mengying Wu Qiuyu Meng Chen Wang Yanan Lu Yuxin Yang Xiaonan Li Qidi Zheng Hu Pu Xin Gui Tianming Li Jiao Li Song Jia Dongdong Lu Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a Molecular Cancer Lnc RNA HULC PTEN Autophagy miR15a |
| title | Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a |
| title_full | Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a |
| title_fullStr | Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a |
| title_full_unstemmed | Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a |
| title_short | Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a |
| title_sort | long noncoding rna hulc accelerates liver cancer by inhibiting pten via autophagy cooperation to mir15a |
| topic | Lnc RNA HULC PTEN Autophagy miR15a |
| url | http://link.springer.com/article/10.1186/s12943-018-0843-8 |
| work_keys_str_mv | AT xiaoruxin longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a AT mengyingwu longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a AT qiuyumeng longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a AT chenwang longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a AT yananlu longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a AT yuxinyang longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a AT xiaonanli longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a AT qidizheng longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a AT hupu longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a AT xingui longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a AT tianmingli longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a AT jiaoli longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a AT songjia longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a AT dongdonglu longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a |