MicroRNA‑873 targets HOXA9 to inhibit the aggressive phenotype of osteosarcoma by deactivating the Wnt/β‑catenin pathway
Authors: Yilin Liu
Liang Zhao
Yuqiang Wang
Hao Yang
Limin Wang
Hongyu Tan
Ruipeng Song
Journal: International Journal of Oncology (2019)
Discipline: CLINICAL MEDICINE
Keywords: miR-873; osteosarcoma; tumor suppressor; oncogenic roles; therapeutic targets
Affiliations: Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.

Abstract:  Several microRNAs (miRNAs or miRs) that regulate a variety of cancer‑related events are dysregulated in osteosarcoma (OS). An exploration of the specific roles of miRNAs in OS is crucial for the identification of suitable therapeutic targets. Previous studies have shown that miR‑873 plays tumor suppressive or oncogenic roles in different types of cancer. However, whether miR‑873 is implicated in OS carcinogenesis and cancer progression remains poorly understood. In the present study, we demonstrated that the miR‑873 levels were decreased in OS tissues and cell lines. The decreased expression of miR‑873 was related to tumor size, clinical stage and distant metastasis in patients with OS. The introduction of miR‑873 significantly inhibited tumor cell proliferation, migration and invasion in vitro, promoted apoptosis in vitro and restricted tumor growth in vivo. Furthermore, homeobox A9 (HOXA9) was validated as a direct target gene of miR‑873 in OS cells. HOXA9 was markedly expressed in OS tissues, and its upregulation inversely correlated with the miR‑873 levels. Moreover, HOXA9 silencing produced similar effects as observed with miR‑873 overexpression in OS cells. Consistently, the exogenous expression of HOXA9 partially reversed the suppression of the aggressive phenotype induced by miR‑873 overexpression in OS cells. Notably, miR‑873 was able to deactivate the Wnt/β‑catenin pathway in OS cells by regulating HOXA9, both in vitro and in vivo. On the whole, the present study demonstrates that miR‑873 suppresses the development of OS by directly targeting HOXA9 and inhibiting the Wnt/β‑catenin pathway, and suggests that miR‑873 may prove to be useful as a diagnostic biomarker of OS, as well as in the development of novel therapies. 

Retracted: No

PubPeer comments:
 Figs 2D, 5D, 6D. ![file] The khaki box marks a panel that also appears in Figs 2D, 5D, 6D of [Yun et al (2016)] . ![file] ![file] Black box marks a panel that also appears in Figs 2C, 4C, 5C of [Zhao Li (2019)] . ![file] ![file] There may be matches with other panels, or with other papers within this oeuvre. https: docs.google.com spreadsheets d 1X401JM6CcpTSkbKsPsOl20pRKQ-ns1S_J5pTwtBjqPw edit#gid=0 , 
 *[above]* Fig 6G from  MicroRNA-664 targets paired box protein 6 to inhibit the oncogenicity of pancreatic ductal adenocarcinoma ([Wang et al 2019] ). *[below]* Fig 7A. ![file] , 
 #2 I missed a second overlap between panels of the two Figures: ![file]  MicroRNA-664 targets paired box protein 6 to inhibit the oncogenicity of pancreatic ductal adenocarcinoma (Wang et al 2019) is now retracted. , 
 - *[left]* **Fig 3B**. - *[middle]* Fig 5J from  Long Noncoding RNA LINC01426 Sequesters microRNA-519d-5p to Promote Non-Small Cell Lung Cancer Progression by Increasing ETS1 Expression ([Dai et al 2020] ). - *[right]* Fig 5D from  Long Noncoding RNA SNHG7, a Molecular Sponge for microRNA-485, Promotes the Aggressive Behavior of Cervical Cancer by Regulating PAK4 ([Wu et al 2020] ) **[retracted]**. ![file] , 
 Retracted [12 September 2022] .  Following the publication of this paper, it was drawn to the Editors 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 migration assay data shown in Fig. 7A, 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 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. ,