MicroRNA-511 inhibits malignant behaviors of breast cancer by directly targeting SOX9 and regulating the PI3K/Akt pathway
Authors: Weifeng Pang
Ling Hao
Lei Wang
Yuying Zhao
Ning Yang
Journal: International Journal of Oncology (2018)
Discipline: CLINICAL MEDICINE
Keywords: miRNA; breast cancer; tumorigenesis; progression; diagnosis
Affiliations: Department of Medical Oncology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.

Abstract:  Numerous studies have revealed that a subset of microRNAs (miRNAs) is aberrantly expressed in breast cancer. The dysregulation of miRNAs is involved in the tumorigenesis and progression of breast cancer due to their negative regulation of downstream target genes. Therefore, the identification of deregulated miRNAs in breast cancer may provide important insights into the diagnosis and treatment of patients with this disease. miRNA‑511 (miR‑511) has been identified to be deregulated in diverse human cancer types; however, neither the expression status nor the detailed roles of miR‑511 in breast cancer have been clarified. Thus, it was aimed to determine the expression of miR‑511 in breast cancer, examine the role in malignant progression and explore its downstream targets. The results of the present study revealed that the expression of miR‑511 was downregulated in breast cancer tissues and cell lines. Decreased expression of miR‑511 was significantly associated with lymph node metastasis and tumor stage in patients with breast cancer. Functional analyses revealed that restoring miR‑511 expression suppressed breast cancer cell proliferation and colony formation, promoted apoptosis and reduced metastasis in vitro, while it attenuated tumor growth in vivo. Additionally, it was revealed that SRY‑box 9 (SOX9) was a direct target gene of miR‑511 in breast cancer cells. SOX9 was upregulated in breast cancer tissues and its expression was inversely correlated with that of miR‑511. Furthermore, SOX9 inhibition simulated the tumor‑suppressive roles of miR‑511 overexpression in breast cancer cells, while SOX9 reintroduction partially rescued these effects of miR‑511. Notably, the upregulation of miR‑511 targeted SOX9 to deactivate the PI3K/Akt signaling in breast cancer in vitro and in vivo. In conclusion, miR‑511 was downregulated in breast cancer, and impeded its malignant progression by directly targeting SOX9 and regulating the PI3K/Akt pathway. Thus, miR‑511 is a potential therapeutic target in breast cancer. 

Retracted: No

PubPeer comments:
 Figs 2D, 5D, 6D.  Apoptosis of MCF-7 and MDA-MB-231 cells following transfection with miR-511 mimics or miR-NC was measured using flow cytometry analysis ;  flow cytometry analysis were performed to assess the ... apoptosis of MCF-7 and MDA-MB-231 cells, respectively, following transfection with SOX9 siRNA or NC siRNA ;  flow cytometry analysis were performed to assess the proliferation, colony formation and apoptosis of MCF-7 and MDA-MB-231 cells, respectively, following transfection with SOX9 siRNA or NC siRNA . ![file] Purple box marks a matching panel in Figs 2C, 4C, 5D of [Lyu et al (2019)] . ![file] ----------------------------------------------- Yellow box marks a matching panel in Figs 2D, 5D of [Liu, Wang Zhao (2017)] . ![file] -------------------------------------------- Grey box marks a matching panel in Figs 2D, 5D, 6D of [Zhao, Xu Zhang (2017)] . ![file] , 
 Figs 2D, 5D, 6D again. ![file] Bright pink box added to mark a matching panel in Figs 2D, 5D, 6D of [Wang et al (2017)] . ![file] ![file] Vermilion and grey box mark matching panels in FIgs 2D, 5D of [Hu, Jin Wang (2018)] . ![] ------------------------------------- Brown box: matching panel in Figs 2G H, 5F G, 6F G of [Liang et al (2017)] . ![file] ![file] , 
 Another panel match with Figs 2G,H and 4G,H from [Ji et al (2017)] . ![] Here in context: ![] ------------------------------------------------------ ![] , 
 *[right]* Fig 8A.  Representative images of the miR-511 mimics-transfected and miR-NC-transfected isolated xenograft tumors. Rotated through 90 deg for convenience. *[left]* Fig 7A from [Li et al (2019)] .  Representative images of tumor xenografts obtained from miR-936 mimics and miR-control groups . I have concerns. ![file] , 
 Retracted [30 August 2022] .  Following the publication of this paper, it was drawn to the Editorsu2019 attention by a concerned reader that various panels showing the data from flow cytometry experiments in Figs. 2D, 5D and 6D, and certain of the tumor images shown in Fig. 8A, were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published, or were already under consideration for publication elsewhere, prior to its submission to International Journal of Oncology, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. ,