MicroRNA-338-3p functions as tumor suppressor in breast cancer by targeting SOX4
Authors: Hongyan Zhang
Qingjie Ma
Ying Jin
Qing Wang
Qian Xie
Min Zhao
Journal: International Journal of Oncology (2015)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNA-338-3p; breast cancer; tumor suppressor; SOX4; metastasis
Affiliations: Department of Ultrasonography, China-Japan Union Hospital of Jilin University, Nanguan District, Changchun 13033, P.R. China., Department of Nuclear Medicine, China-Japan Union Hospital of Jilin University, Nanguan District, Changchun 13033, P.R. China., Department of Oncology and Hematology, China-Japan Union Hospital of Jilin University, Nanguan District, Changchun 13033, P.R. China., Department of Endocrinology, China-Japan Union Hospital of Jilin University, Nanguan District, Changchun 13033, P.R. China.

Abstract:  MicroRNA-338-3p (miR‑338-3p), a recently discovered miRNA, has been reported to be downregulated and play tumor suppressor roles in gastric cancer, ovarian cancer, colorectal carcinoma and lung cancer by targeting several genes. However, the role and potential mechanism of miR‑338-3p in breast cancer (BC) is still unclear. In the present study, we investigated the roles and mechanisms of miR‑338-3p in human breast cancer. miR‑338-3p expression was determined by qRT-PCR in human BC cell lines, and clinical significantly of miR‑338-3p expression was further evaluated. Furthermore, the function of miR‑338-3p in breast cancer also was investigated by several in vitro approaches and in nude mouse models. Luciferase assay and western blot analysis were performed to validate the potential targets of miR‑338-3p after the preliminary screening by employing open access software. It was found that miR‑338-3p was significantly downregulated in both BC tissues and cell lines and the low expression of miR‑338-3p was inversely correlated with lymph node metastatic and TNM stage status (P&lt;0.01). Function assay showed that the overexpression of miR‑338-3p in BC cells significantly inhibited cell proliferation, colony formation, migration and invasion, and induced cell apoptosis and cell cycle arrest at G1/G0 stage, as well as suppressed tumor growth in the nude mouse model. Luciferase assay and western blot analysis identified sex-determining region Y-box 4 (SOX4) as a direct and functional target of miR‑338-3p. These findings revealed that miR‑338-3p may act as a tumor suppressor in breast cancer by targeting SOX4, suggesting miR‑338-3p as a novel strategy for breast cancer treatment. 

Retracted: No

PubPeer comments:
 Fig 3A.  Cell migration of MDA-MB-231 cells transfected with miR-338-3p mimic was determined with wound-healing assay . ![file] Fig 5D from [Li et al (2017)] . Cell  migration ... in SKOV3 cells transfected with miR-218 mimic or miR-NC with or without RUNX2 overexpression plasmid . ![file] , 
 Fig 6B.  Western blot analysis of SOX4 expression in human breast cancer tissue samples (BC) and their matched normal breast tissues (NB) . ![file] The loading control appears in a long series of papers by different authors - sometimes as GAPDH and sometimes as beta-actin. E.g. Fog 6A from [Liu et al (2016)] . More examples are linked in that thread. ![] (note the similarities in the substantive band as well). , 
 *[above]* Fig 5D.  The expression of SOX4 protein was determined by western blot assay . *[below]* Fig 4A from [Lin et al (2015)] .  SKOV3 cells and HEY cells were treated with TRAIL alone, Lv sh-NOB1 alone, or the combination for 24 h. The anti-apoptosis protein, survivin and Bcl-2 protein expression were examined by Western blot using corresponding antibodies. ![file] , 
 *[left]* Fig 4B. Cell apoptosis  determined by flow cytometry in MDA-MB-231 cells after transfection with miR-338-3p mimic and determined with wound healing assay [???] . *[right]* Fig 2E from [Zhang et al (2016)] .  Cell apoptosis was determined in 786-O cells transfected with miR-22 mimic or miR-NC by FACS analysis . ![file] Could the authors of either paper explain the appearance of the same FACS plots in both? , 
 *[below]* Fig 4A.  Cell cycle ... determined by flow cytometry in MDA-MB-231 cells after transfection with miR-338-3p mimic and determined with wound healing assay [??] *[above]* Fig 3A from [Liu et al (2015)] .  Cell cycle was analyzed by FACS in HepG2 cells transfected with miR-132 mimic or miR-control. Surprisingly similar. ![file] ,