MicroRNA-664 targets paired box protein 6 to inhibit the oncogenicity of pancreatic ductal adenocarcinoma
Authors: Songsong Wang
Songtao Niu
Xiaoya Wang
Jiaqi Wang
Qi Wang
Yibin Liu
Journal: International Journal of Oncology (2019)
Discipline: CLINICAL MEDICINE
Keywords: miRNA-664; pancreatic ductal adenocarcinoma; PAX6; tumor suppression; oncogenic
Affiliations: Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China., Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.

Abstract:  The abnormal expression of microRNAs (miRNAs or miRs) with oncogenic or tumor‑suppressive roles in pancreatic ductal adenocarcinoma (PDAC) has been widely reported in recent years, and these dysregulated miRNAs are implicated in the formation and progression of PDAC. Therefore, an investigation into the functional roles of miRNAs in PDAC may facilitate the identification of effective therapeutic targets. miRNA‑664 (miR‑664) has been found to be aberrantly expressed and to play crucial roles in several human cancer types. However, the expression pattern and functional roles of miR‑664 in the malignant capacity of PDAC have yet to be elucidated. In this study, the results revealed that miR‑664 was clearly downregulated in PDAC tissues and cell lines. The low miR‑664 expression was strongly associated with pathological T stage and lymph node metastasis of the patients with PDAC. Patients with PDAC with a low miR‑664 expression had a poorer overall survival and a worse disease‑free survival than those patients with a high miR‑664 level. Functional experiments suggested that exogenous miR‑664 expression suppressed the growth and metastasis of PDAC cells in vitro, whereas miR‑664 downregulation exerted the opposite effects. In addition, miR‑664 suppressed the tumor growth of PDAC cells in vivo. Mechanistically, paired box protein 6 (PAX6) was identified as a direct target gene of miR‑664 in PDAC cells. Furthermore, PAX6 was upregulated in PDAC tissues, and its upregulation inversely correlated with miR‑664 levels. Moreover, the silencing of PAX6 mimicked the effects of miR‑664 upregulation in PDAC cells, and the recovered expression of PAX6 eliminated the effects of miR‑664 on PDAC cells. Notably, miR‑664 could inhibit the activation of PI3K/Akt pathway in PDAC cells in vitro and in vivo. Cumulatively, these results indicate an important role of the miR‑664/PAX6 pathway in suppressing the aggressiveness of PDAC cells, suggesting that miR‑664 may be an attractive therapeutic target for the treatment of patients with this fatal disease. 

Retracted: Yes

PubPeer comments:
 Figs 2D, 5D, 6E.  The rate of apoptotic cells was determined by flow cytometric analysis ;  Apoptotic rate of Panc-1 and SW1990 cells treated as above was detected by flow cytometry ;  The apoptotic rate was analyzed by flow cytometry . ![file] Colored boxes indicate panels which match panels in other, unrelated papers. Two panels are the same (khaki boxes) and along with the teal-marked panel, they have matches in 2D,5D,6D of [Kang et al (2018)] . ![file] Black box matches a panel of Figs 2D, 5D, 6D of [Wang et al (2017)] . ![file] , 
 #1 Figs 2D, 5D, 6E again ![file] Magenta box matches a panel from [Lyu et al (2019)] (down in bottom left corner). ![file] Finally, for medium-blue panel, see Figs 3B,5D of [Shen et al (2017)] . ![] Also Figs 2D, 5D, 6D from [Zhao, Xu Zhang (2017)] . ![] , 
 Unexpected similarity between a panel of the present paper, and one from [Song et al (2018)] . ![file] Figs 2D, 5D, 6E from here, for context: ![file] Figs 2D, 4D, 5D from Song et al (2019): ![file] , 
 Figs 2D, 5D, 6E again. ![] Two panels matches two from [Chen et al (2019)] . ![] ----------------------------------------------------------- Here in context. ![] , 
 Figs 2D, 5D, 6E again. ![] Maroon box marks a panel that is shared with Figs 2C, 5C, 6C of [Song et al (2019)] . ![] , 
 *[above]* Fig 7. *[below]* Fig 4A from  MicroRNAu2011212 inhibits colorectal cancer cell viability and invasion by directly targeting PIK3R3 ([Zhang et al 2017] ). Two Western Blot bands are unexpectedly similar. H t ImageTwin. ![file] , 
 *[above]* Fig 6G. *[below]* Fig 7A from  MicroRNAu2011873 targets HOXA9 to inhibit the aggressive phenotype of osteosarcoma by deactivating the Wnt u03b2u2011catenin pathway ([Liu et al 2019] ). ![file] , 
 In two columns: - **Fig 5E F**. - Figs 2F; 4D E from  Long noncoding RNA NR2F1-AS1 enhances the malignant properties of osteosarcoma by increasing forkhead box A1 expression via sponging of microRNA-483-3p ([Li et al 2019] ). - Fig 5E from  microRNA-612 suppresses the malignant development of non-small-cell lung cancer by directly targeting bromodomain-containing protein 4 ([Kang et al 2019] ). - Fig 7H from  LINC00511 promotes the malignant phenotype of clear cell renal cell carcinoma by sponging microRNA-625 and thereby increasing cyclin D1 expression ([Deng et al 2019] ). - Fig 5C from  MicroRNAu2011877 inhibits cell proliferation and invasion in nonu2011small cell lung cancer by directly targeting IGFu20111R ([Zhou et al 2019] ). ![] , 
 Retracted [6 June 2022] .  Following the publication of this paper, it was drawn to the Editors attention by a concerned reader that several of the panels showing flow cytometric assay data in Figs. 2D, 5D and 6E, western blotting data featured in Fig. 7, and certain of the cell migration assay data panels included in Fig. 5E and F and Fig. 6G 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 elsewhere, or were already under consideration for publication, 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. ,