This preprint is under consideration at Cancer Cell International. A preprint is 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.
Learn more about In Review
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
Research Article
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Introduction: Huge amounts of gene-sequencing data have been used to guide fundamental researches. The study combined bioinformatics tools with basic study to analyze the pathological mechanisms of diffuse large B-cell lymphoma.
Methods: A LncRNA-miRNA-mRNA ceRNA network of diffuse large B cell lymphoma was constructed by GTEx combined with TCGA database analysis. qPCR was used to detect the expression of LINC00963 and miR-320a in DLBCL cell lines. The proteins levels of UPR sensors, GRP78, p-IRE1α, IRE1α, active ATF6, ATF4 and XBP1, were assessed through Western blot, along with apoptosis markers (Bcl-2, Bax, caspase 3) and autophagy indicators (Beclin1, LC3II, LC3I and p62) after LINC00963 overexpression or miR-320a overexpression in vitro. Additionally, the expression of LC3 was analyzed through immunofluorescence (IF) assay.
Results: Evaluation of SUDHL4 cell showed marked up-regulation of key elements of the UPR (GRP78, p-IRE1α, spliced XBP-1(XBP-1(s))), apoptosis (Bax, cleaved caspase 3) and autophagy (Beclin1, LC3II) after LINC00963 overexpression in vitro, whereas miR-320a mimic reversed the effects. Besides, LINC00963 targeted miR-320a while miR-320a bound to the 3’UTR of XBP1. The work also found that LINC00963 overexpression resulted in significant tumor growth delay in a xenograft model of DLBCL.
Conclusion: Mechanistically, LINC00963 / miR-320a regulated XBP1-apoptosis pathway and autophagy, making this pathway an attractive therapeutic target for selective targeting. The data presented here are the first to comprehensively survey the mechanism of LINC00963 / miR-320a/XBP1 in DLBCL.
Keywords
Bioinformatics, LINC00963, miR-320a, XBP1, ERs, apoptosis, autophagy
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
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 01 Apr, 2021
No community comments so far
Editorial decision: Major revision
On 04 May, 2021
Review #2 received
Received 03 May, 2021
Review #1 received
Received 18 Apr, 2021
Reviewer #3 agreed
On 15 Apr, 2021
Review #3 received
Received 15 Apr, 2021
Reviewer #2 agreed
On 12 Apr, 2021
Reviewer #1 agreed
On 09 Apr, 2021
Reviews received
Received 09 Apr, 2021
Reviewers invited
Invitations sent on 29 Mar, 2021
Editor assigned
On 21 Mar, 2021
Submission checks complete
On 21 Mar, 2021
Editor invited
On 21 Mar, 2021
First submitted
On 21 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Learn more about our company.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
This preprint is under consideration at Cancer Cell International. A preprint is 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.
Learn more about In Review
Research Article
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 01 Apr, 2021
No community comments so far
Editorial decision: Major revision
On 04 May, 2021
Review #2 received
Received 03 May, 2021
Review #1 received
Received 18 Apr, 2021
Reviewer #3 agreed
On 15 Apr, 2021
Review #3 received
Received 15 Apr, 2021
Reviewer #2 agreed
On 12 Apr, 2021
Reviewer #1 agreed
On 09 Apr, 2021
Reviews received
Received 09 Apr, 2021
Reviewers invited
Invitations sent on 29 Mar, 2021
Editor assigned
On 21 Mar, 2021
Submission checks complete
On 21 Mar, 2021
Editor invited
On 21 Mar, 2021
First submitted
On 21 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Introduction: Huge amounts of gene-sequencing data have been used to guide fundamental researches. The study combined bioinformatics tools with basic study to analyze the pathological mechanisms of diffuse large B-cell lymphoma.
Methods: A LncRNA-miRNA-mRNA ceRNA network of diffuse large B cell lymphoma was constructed by GTEx combined with TCGA database analysis. qPCR was used to detect the expression of LINC00963 and miR-320a in DLBCL cell lines. The proteins levels of UPR sensors, GRP78, p-IRE1α, IRE1α, active ATF6, ATF4 and XBP1, were assessed through Western blot, along with apoptosis markers (Bcl-2, Bax, caspase 3) and autophagy indicators (Beclin1, LC3II, LC3I and p62) after LINC00963 overexpression or miR-320a overexpression in vitro. Additionally, the expression of LC3 was analyzed through immunofluorescence (IF) assay.
Results: Evaluation of SUDHL4 cell showed marked up-regulation of key elements of the UPR (GRP78, p-IRE1α, spliced XBP-1(XBP-1(s))), apoptosis (Bax, cleaved caspase 3) and autophagy (Beclin1, LC3II) after LINC00963 overexpression in vitro, whereas miR-320a mimic reversed the effects. Besides, LINC00963 targeted miR-320a while miR-320a bound to the 3’UTR of XBP1. The work also found that LINC00963 overexpression resulted in significant tumor growth delay in a xenograft model of DLBCL.
Conclusion: Mechanistically, LINC00963 / miR-320a regulated XBP1-apoptosis pathway and autophagy, making this pathway an attractive therapeutic target for selective targeting. The data presented here are the first to comprehensively survey the mechanism of LINC00963 / miR-320a/XBP1 in DLBCL.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Loading...