This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Primary research
Xinhua Zhu
Affiliated Drum Tower Hospital, Medical of Nanjing University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8162-6771
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high mortality and poor prognosis. Long non-coding RNAs NEAT1 (lncRNA NEAT1) have been found to play an important role in HCC progression. However, the role and potential molecular mechanism of lncRNA NEAT1 in HCC remain largely unclear.
Methods
The role of lncRNA NEAT1 both in vitro and in vivo was investigated, with RNA pull-down and RNA immunoprecipitation (RIP) assays being performed to determine the interaction among NEAT1 and FOXO3 and PKM2. In addition, HCC cells were treated with exosomes derived from NEAT1-overexpressing HCC cells, and then cell proliferation, migration and invasion were assessed using in vitro assays.
Results
In this study, overexpression of NEAT1 promoted the proliferation, migration and invasion of HCC cells, whereas NEAT1 knockdown exhibited the opposite effects. Mechanistically, NEAT1 was found to recruit transcription factor FOXO3 to PKM2 promoter region and upregulate PKM2 expression. Meanwhile, overexpression of NEAT1 increased tumor growth and metastasis in a mouse xenograft model of HCC in vivo via upregulation of PKM2. Furthermore, overexpression of NEAT1 promoted exosome release from HCC cells. Exosomes secreted from NEAT1-overexpressing HCC cells promoted the proliferation, migration and invasion of HCC cells.
Conclusion
We found that NEAT1 could promote HCC progression via upregulation of PKM2 and exosome-mediated transfer. These data indicated that NEAT1 may be a therapeutic target in HCC.
Keywords
Hepatocellular carcinoma, NEAT1, FOXP3, exosome, PKM2
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Loading...
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 09 Nov, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Learn more about our company.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Primary research
Xinhua Zhu
Affiliated Drum Tower Hospital, Medical of Nanjing University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8162-6771
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 09 Nov, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high mortality and poor prognosis. Long non-coding RNAs NEAT1 (lncRNA NEAT1) have been found to play an important role in HCC progression. However, the role and potential molecular mechanism of lncRNA NEAT1 in HCC remain largely unclear.
Methods
The role of lncRNA NEAT1 both in vitro and in vivo was investigated, with RNA pull-down and RNA immunoprecipitation (RIP) assays being performed to determine the interaction among NEAT1 and FOXO3 and PKM2. In addition, HCC cells were treated with exosomes derived from NEAT1-overexpressing HCC cells, and then cell proliferation, migration and invasion were assessed using in vitro assays.
Results
In this study, overexpression of NEAT1 promoted the proliferation, migration and invasion of HCC cells, whereas NEAT1 knockdown exhibited the opposite effects. Mechanistically, NEAT1 was found to recruit transcription factor FOXO3 to PKM2 promoter region and upregulate PKM2 expression. Meanwhile, overexpression of NEAT1 increased tumor growth and metastasis in a mouse xenograft model of HCC in vivo via upregulation of PKM2. Furthermore, overexpression of NEAT1 promoted exosome release from HCC cells. Exosomes secreted from NEAT1-overexpressing HCC cells promoted the proliferation, migration and invasion of HCC cells.
Conclusion
We found that NEAT1 could promote HCC progression via upregulation of PKM2 and exosome-mediated transfer. These data indicated that NEAT1 may be a therapeutic target in HCC.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Loading...