{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T08:12:02Z","timestamp":1778573522064,"version":"3.51.4"},"update-to":[{"DOI":"10.12688\/f1000research.173746.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000}},{"DOI":"10.12688\/f1000research.173746.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000}}],"reference-count":27,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"This work was partially supported by Southern Technical University under scientific research awards","award":["No.9\/7934"],"award-info":[{"award-number":["No.9\/7934"]}]},{"name":"This work was partially supported by Southern Technical University under scientific research awards","award":["10Sep.2025."],"award-info":[{"award-number":["10Sep.2025."]}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>Background Pancreatic cancer has a poor prognosis and is highly aggressive and deadly. Most pancreatic cancer diagnoses are adenocarcinomas, which account for more than 90 % of all cases. Developing effective therapeutic strategies requires an understanding of the molecular mechanisms associated with pancreatic cancer progression. Small nucleolar RNA H\/ACA Box 64 (SNORA64) was presented as a predictive marker for pancreatic cancer stages in our previous study. SNORA64 showed a gradual loss of its expression throughout the carcinogenesis process, and it inhibited metastasis by interfering with epithelial to mesenchymal transition (EMT). In this study, we investigated the role of SNORA64 on an intrinsic apoptotic pathway in pancreatic cancers by using human pancreatic cell line derived from adenocarcinoma PK-8 with SNORA64 knockdown and the scramble to compare with. Methods QPCR techniques used to measure the gene expression level of apoptosis related genes and cell viability assay using trypan blue exclusion are implanted in this study as investigational methods. Results Pk-8 SNORA64 knockdown shows a significant low expression of tumor suppressor P53 in contrast to the scramble control cell line. Pk-8 SNORA64 knockdown shows significantly high expression of anti-apoptotic genes B-cell leukemia\/lymphoma-2 (BCl2) and B-cell lymphoma-extra-large (BCL-Xl) in contrast to the scramble control cell line. Conversely, the pro-apoptotic genes BH3 interacting domain death agonist (BID), BCL2 Associated X (BAX), and BCL2 homologous antagonist\/killer (BAK) show significantly low expression compared to the scramble control. However, there is no change in the expression of BAD and BIM in Pk-8 with SNORA64 knockdown compared to the scrambled control cell line. Furthermore, the Pk-8 with SNORA64 knockdown shows a significant high proliferation rate and viability percentage compared to the scramble control cell line. Conclusion The downregulation of SNORA64 affects apoptosis pathways by manipulating pro- and anti-apoptotic gene regulators. The SNORA64 interactions with apoptotic inhibitor molecules and downregulation of pro-apoptotic molecules significantly sustain cellular viability. Therefore; SNORA64 may serve as a sensitizer to apoptosis-inducing therapies.<\/ns3:p>","DOI":"10.12688\/f1000research.173746.3","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T07:39:09Z","timestamp":1778571549000},"page":"68","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of Small Nucleolar RNA H\/ACA Box 64 (SNORA64) on Apoptosis Regulator Genes in Pancreatic Cancer in Vitro"],"prefix":"10.12688","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2859-9073","authenticated-orcid":false,"given":"Rana","family":"Alfardan","sequence":"first","affiliation":[{"name":"Community Health Techniques Department Basrah Basrah 61004 Southern Technical University"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"173-181","DOI":"10.4251\/wjgo.v12.i2.173","article-title":"Pancreatic ductal adenocarcinoma: Treatment hurdles, tumor microenvironment and immunotherapy.","volume":"12","author":"P Sarantis","year":"2020 Feb 15","journal-title":"World J. 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I have accepted all of them, and they have significantly enriched my manuscript. Please find below a point-by-point response to your comments:  \n<b>Title:<\/b>&nbsp;Thank you for your valuable suggestion regarding the manuscript title. I agree that the proposed title, \n<b>&quot;Downregulation of SNORA64 Promotes Pancreatic Cancer Cell Survival by Modulating the Apoptotic Regulator Gene Network,&quot;<\/b> would indeed be powerful and appropriate for this work. However, upon further consideration of this modification, I have encountered a significant practical constraint. The data of the manuscript has already been published online under its current title, making a title change procedurally difficult at this stage. Furthermore, the previous two editors involved with this manuscript explicitly endorsed the current title during the review process. Given these circumstances, and with respect for the editorial consistency maintained throughout the review process, I believe the title should remain unchanged. I hope you understand this decision, and I appreciate your understanding regarding this limitation. Sincerely, \n<b>Abstract:<\/b>&nbsp;As suggested, the abstract has been revised to specify the key techniques used. It now also explicitly includes the key findings regarding p53 downregulation and the lack of change in BAD\/BIM. Furthermore, the potential therapeutic implications have been stated more clearly. \n<b>Conclusion:<\/b>&nbsp;The conclusion has been revised exactly as you suggested. \n<b>Introduction:<\/b>&nbsp;Our previous study is already mentioned in the introduction. The text has been revised to directly introduce pancreatic cancer and explicitly motivate the current functional investigation into apoptosis, creating a smoother transition from the background to the study's objective. \n<b>Materials and Methods:<\/b>  \n<b>2.1:<\/b>&nbsp;The transfection of the PK-8 cell line is performed with siRNA oligos carried by psiRNA-h7SKG1. The oligo sequences and the protocol are detailed in the cited reference. However, as you suggested, the type of small RNA used for the knockdown has now been specified in the text. \n<b>2.2:<\/b>&nbsp;The sentence regarding the use of agarose gels for qPCR product verification has been revised as you suggested for clarity. \n<b>Table 1:<\/b>&nbsp;The table format has been changed as you recommended. It now consists of three columns: Gene Symbol, Left Primer, and Right Primer. \n<b>2.4:<\/b>&nbsp;Excel has now been added to the &quot;Materials&quot; subsection as one of the software used for statistical analysis.   \n<b>Results:<\/b>  The results for p53 (3.1) are now presented before the BCL2 family results (3.2), following the logical flow you recommended. \n<b>Figure References:<\/b>&nbsp;All figures (Figure 1, 2A\/B, 3, 4A\/B) are now explicitly called out in the results text in sequential order. \n<b>Language:<\/b>&nbsp;For consistency, the phrasing &quot;PK-8 with SNORA64 knockdown&quot; is now used consistently throughout the manuscript.   \n<b>Discussion:<\/b>  \n<b>Paragraph 1:<\/b>&nbsp;Two sentences have been added to discuss the observed downregulation of p53 and its potential implications. \n<b>Paragraph 2:<\/b>&nbsp;This paragraph now focuses on discussing the BCL2 family, including both pro- and anti-apoptotic molecules. \n<b>Paragraph 3:<\/b>&nbsp;Two sentences have been added to discuss the connection between the caspase cascade and the BCL2 pathway. \n<b>Paragraph 4:<\/b>&nbsp;This paragraph has been rephrased, and three sentences have been added to elaborate on the increase in cell viability. \n<b>Paragraph 5:<\/b>&nbsp;A new paragraph specifically discussing BIM and BAD has been added. \n<b>Mechanistic Speculation:<\/b>&nbsp;Thank you for this excellent suggestion. This section has been incorporated into the revised manuscript (version 2).   \n<b>Limitations:<\/b>&nbsp;A new &quot;Limitations&quot; subsection has been added to the discussion, as you recommended, to address the constraints of the current study.  Thank you again for your time and expertise, which have greatly improved the quality of my work.  Sincerely, Dr. Rana Alfardan","URL":"https:\/\/f1000research.com\/articles\/15-68\/v3#referee-comment-15669","order":1,"name":"referee-comment-15669","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.197739.r470979, Tingbo Liang, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 10 Apr 2026, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/15-68\/v2#referee-response-470979","order":2,"name":"referee-response-470979","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.197739.r471177, Ramina Khoshaba Elia, University of Baghdad, Baghdad, Baghdad Governorate, 17 Apr 2026, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/15-68\/v2#referee-response-471177","order":3,"name":"referee-response-471177","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.197739.r471178, Dheyaa Al-Sallami, Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois, 20 Apr 2026, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/15-68\/v2#referee-response-471178","order":4,"name":"referee-response-471178","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was partially supported by Southern Technical University under scientific research awards, No. 9\/7934, 10 Sep. 2025. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":5,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}