MicroRNA-27 Inhibits Autophagy and Promotes Proliferation of Multiple Myeloma Cells by Targeting the NEDD4/Notch1 Axis
Authors: Jiao Chen
Feifei Che
Xiaobing Huang
Chunqian Wan
Journal: Frontiers in Oncology (2020)
Discipline: CLINICAL MEDICINE
Keywords: NEDD4; Notch1; autophagy; invasion; miR-27
Affiliations: Department of Hematology, Sichuan Academy of Medical Science & Sichuan People's Hospital, Chengdu, China.

Abstract:  Multiple myeloma (MM) is a malignant tumor disease that seriously affects the health of patients. Previous studies have shown the crucial role of autophagy in the development of MM. Therefore, the study aimed to study the effect of miR-27 on autophagy in MM via NEDD4/Notch1 axis. RT-qPCR or western blot analysis was used to detect the expression of miR-27, NEDD4, and Notch1 in bone marrow tissues and CD138+ plasma cells of patients and MM cells. After gain- and loss-of-function assays in MM cells, proliferation and invasion were assessed by clone formation and Transwell assays. Meanwhile, expression of autophagy-related proteins was measured by western blot analysis, followed by evaluation of autophagosomes and autophagic flow. The targeting relationship was evaluated by luciferase reporter assay, whereas the binding of NEDD4 to Notch1 protein was analyzed by co-immunoprecipitation. The ubiquitination level of Notch1 protein was detected. A nude mouse tumor model was established to determine the role of miR-27 in MM in vivo. miR-27 and Notch1 upregulation and NEDD4 downregulation were observed in bone marrow tissues and CD138+ plasma cells of patients and MM cells. miR-27 negatively targeted NEDD4, while NEDD4 could specifically bind to Notch1 protein to increase Notch1 ubiquitin degradation in MM cells. miR-27 or Notch1 overexpression or NEDD4 silencing diminished autophagy but enhanced proliferation and invasion of MM cells. miR-27 upregulation promoted the formation of subcutaneous tumor in nude mice. Collectively, miR-27 elevated Notch1 expression by targeting NEDD4 and promoted the development of MM by inhibiting cell autophagy, which provides a new idea and basis for MM treatment. 

Retracted: Yes

PubPeer comments:
 *[below]* Figure 3C from [Niu et al (2018)] .  Linc-UBC1 inhibition suppressed migration and invasion of ESCC cells. ... (C-D) Transwell assay demonstrated that the number of invaded cells was significantly reduced in sh-linc-UBC1 cells compared with sh-ctrl cells. *[above]* Figure 2F from [Yu, Zhao He (2018)] . Knockdown of PVT1 decreased colon cancer cell proliferation and invasion. ... (E) Transwell assay showed that the number of invaded cells in sh-PVT1 group was obviously reduced compared with sh-ctrl group. How did two nominally-unrelated teams of researchers come to use the same invasion-assay panel? ![file] , 
 Fig 3A.  Linc-UBC1 inhibition suppressed migration and invasion of ESCC cells. (A-B) Wound healing assay showed that knockdown of linc-UBC1 significantly suppressed the migration ability in sh-linc-UBC1 cells compared with sh-ctrl cells. ![file] One of these panels (red rectangle) is a manifestation of a papermill s stock image of wound-healing labelled  WH04 [by Elisabeth Bik] . ![file] Another (blue rectangle) is a manifestation of the  WH12 wound-healing stock image. ![file] I did not attempt to match the other panels. , 
 This paper is one of a set of now 124 papers that all contain images from the same library of about 100 photos and plots. This is unexpected, because each paper has different authors and different affiliations, with little to no overlap, and describes different cancer types and molecules. It would be very hard to explain how authors from different labs would all obtain the same photo. Therefore, the papers might have all be derived from the same source, such as a paper mill that sells ready-to-be-published papers. This  Stock Photo paper set has been described in more detail on my blog post, https: scienceintegritydigest.com 2020 07 05 the-stock-photo-paper-mill and in a Wall Street Journal article by Eva Xiao (currently behind a paywall): https: www.wsj.com articles chinese-research-papers-raise-doubts-fueling-global-questions-about-scientific-integrity-11593939600 The vast majority (113 124) of the papers were published in the same journal, European Review for Medical and Pharmacological Sciences (ERMPS). Six papers from this set, including this one, were publihed in JBUON. A link to the full set of papers can be found here: https: docs.google.com spreadsheets d 172RWS18w1lTNJ9Nnj80fuXXTqTm4fGkoK0sdYyvKE3g edit?usp=sharing The 121 initially found papers have been reported to the journal editors on July 2, 2020. , 
 I thank Hoya Camphorifolia for letting me know about this paper. To further illustrate my comment in #3, here are Figure 4A and 4C again, with in red the names of the stock photos that the panels correspond to. I could match three of the wound healing assay photos and three of the transwell assay photos to those used in the other Stock Photo paper mill papers. ![file] Here, for example is the collage of  TW12, The Lion King , which matches the left most panel in Figure 3C. ![file] And here is  TW14, Necklace Whale SharkEgg SoundBarrier , to which the third panel in Figure 3C matches, if it is turned upside down. ![file] The original PDF has been archived here: https: web.archive.org web 20210211044115 https: www.jbuon.com archive 23-1-157.pdf ,