HNF1A‑AS1 promotes growth and metastasis of esophageal squamous cell carcinoma by sponging miR‑214 to upregulate the expression of SOX-4
Authors: Wencai Li
Xianzheng Gao
Yanping Zhang
Guannan Wang
Dandan Zhang
Ye Li
Wugan Zhao
Journal: International Journal of Oncology (2017)
Discipline: CLINICAL MEDICINE
Keywords: Esophageal squamous cell carcinoma; HNF1A-AS1; lncRNA; cell proliferation; apoptosis
Affiliations: Department of Pathology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.

Abstract:  Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies in the world, marked by dysphagia and weight loss, bringing great suffering to patients. HNF1A‑AS1 (HAS1), a long non-coding RNA (lncRNA), has been identified prevalently involved in various human cancers. However, the exact effects and molecular mechanisms of HAS1 in ESCC progression are still elusive. In this study, upregulated expression of HAS1 was detected in ESCC tissues and four human ESCC cell lines (KYSE70, KYSE450, EC109 and EC970) compared with normal tissues and cell lines. Small interfering RNA (siRNA)-mediated knockdown of HAS1 largely suppressed cell proliferation and promoted cell apoptosis in KYSE70 and EC109 cells. The decreased expression of proliferation marker proteins and elevated level of apoptosis marker proteins further verified that HAS1‑siRNA suppressed cell viability in ESCC cells. Besides, the silence of HAS1 strongly reduced the wound closing rate and the number of invasive cells compared with control group. HAS1-siRNA also restrained the expression of migration marker proteins matrix metalloproteinase-9 (MMP-9) and vascular endothelial cell growth factor (VEGF). In addition, miR‑214 was predicted as a direct target of HAS1 by bioinformatics analysis. Downregulated expression of miR‑214 was elevated in KYSE70 and EC109 cells transfected with HAS1-siRNA. Subsequently, elevated expression of miR‑214 was suppressed by co-transfecting with miR‑214 inhibitor in EC109 cells pretreated with HAS1-siRNA. The result of luciferase activity assay showed that luciferase activity was strongly weakened by the combination of LncR-HAS1 WT and miR‑214 mimic. Moreover, the expression of SOX-4, a predicted target gene of miR‑214, was suppressed by HAS1-siRNA and was increased by miR‑214 inhibitor. HAS1-siRNA counteracted the effect of miR‑214 inhibitor on cell viability and mobility in EC109 cells. Finally, the in vivo experiment revealed that HAS1-siRNA abated the role of miR‑214 inhibitor in promoting tumor growth and metastasis. miR-214 also mediated the effect of HAS1 on upregulating the expression of SOX-4 in vivo. Taken together, our study indicated a HAS1-miR‑214-SOX-4 pathway in regulating the growth and metastasis of ESCC, providing a promising target for ESCC therapy. 

Retracted: Yes

PubPeer comments:
  Figure 3. Inhibition of HAS1 suppresses cell motility. KYSE70 and EC109 cell lines were transfected with HAS1-siRNA or siRNA scramble, respectively. (A) Transwell invasion assay was conducted to observe the invasive cells in KYSE70 and EC109 cells.  ![file] Possibly this figure was a test to see if any of the peer reviewers at IJO were paying attention. , 
 #1 After rotation, the HAS1-siRNA panels reward comparison with the LV-MEG3 panels of Fig 2C and FIg 4A from [Li et al (2018)] . ![file] ![file] A detail manifested in Fig 2A of [Gu et al (2019)] . ![] , 
 Please be noted, the same or very similar crease of Surgical pad are showing on the following 11 chinese papers including this paper. Also, the samples on the pad are somehow shared in those papers. UCA1 Regulates the Growth and Metastasis of Pancreatic Cancer bySponging miR-135a. Oncology research (2017) . DOI: 10.3727 096504017x14888987683152. ![file] H19 promotes the migration and invasion of colon cancer by spongingmiR-138 to upregulate the expression of HMGA1. INTERNATIONAL JOURNAL OF ONCOLOGY (2017). DOI: 10.3892 ijo.2017.3941. ![file] Silencing of lncRNA CCDC26 Restrains the Growth and Migration of Glioma Cells In Vitroand In Vivo via Targeting miR-203. Oncology research (2018). DOI: 10.3727 096504017x14965095236521. ![file] Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancervia Targeting miR-198 and Promoting the MAPK1 Pathway. Oncology research (2018) . DOI: 10.3727 096504017x14944585873631. ![file] HOTAIR contributes to cell proliferation and metastasis of cervical cancer via targetting MAPK1 axis. Bioscience reports (2018). DOI: 10.1042 bsr20171563. ![file] Long non-coding RNA MEG3 inhibits cell growth of gliomas by targeting miR-93 andinactivating PI3K AKT pathway. Oncology reports (2017). DOI: 10.3892 or.2017.5871. ![file] The inhibitory effect of MEG3 miR-214 AIFM2 axis on the growth of T-cell lymphoblastic lymphoma. INTERNATIONAL JOURNAL OF ONCOLOGY. DOI: 10.3892 ijo.2017.4006. ![file] Inhibition of BAMBI reduces the viability and motility of colon cancervia activating TGFu2011u03b2 Smad pathway in vitro and in vivo. ONCOLOGY LETTERS. 10.3892 ol.2017.6811. ![file] HNF1Au2011AS1 promotes growth and metastasis of esophageal squamous cellcarcinoma by sponging miRu2011214 to upregulate the expression of SOX-4. INTERNATIONAL JOURNAL OF ONCOLOGY. DOI: 10.3892 ijo.2017.4034. ![file] Astragaloside IV inhibits progression of glioma via blocking MAPK ERKsignaling pathway. Biochemical and Biophysical Research Communications (2017). DOI: 10.1016 j.bbrc.2017.07.052. ![file] Epigenetic silence of HOTAIR contributes to the metastasis of pancreaticcancer via targeting miR-138. Oncology Research (2017). DOI: 10.3727 096504017X15138544374391. ![file] Possibly the following one: Long Noncoding RNA MEG3 Inhibits Cell Proliferation and Metastasis in Chronic Myeloid Leukemia via Targeting miR-184. Oncology research (2018) . DOI: 10.3727 096504017x14980882803151 ![file] , 
 A scatterplot based on the same points is used in Fig 5E of [Li et al (2018)] , Fig 6D of [Zhang et al (2017)] , Fig 1C of [Chen et al (2019)] , Fig 3K of [Yang et al (2017)] , Fig 7A of [Fan et al (2017)] and Fig 5H of [Wang et al (2017)] . ![file] This deserves some sort of award. , 
 Retracted [11 January 2021] . ------------------------------ Following the publication of this paper, it was drawn to the authors attention by an interested reader that the Transwell invasion assay images in Fig. 3A had been duplicated and re-presented within the same Figure. Furthermore, the same data were strikingly similar, in spite of their different presentation, to data featured in Fig. 2A of an article appearing in Oncology Research [Gu J, Cui, C-F, Yang, L, Wang L and Jiang X-H: Emodin inhibits colon cancer cell invasion and migration by suppressing epithelial-mesenchymal transition via the Wnt u03b2-catenin pathway. Oncol Res 27: 193-202, 2019]. Finally, some of the tumour images featured in Fig. 6A of the above paper were strikingly similar to those featured in several other publications. The Editor asked the authors for an explanation to account for the appearance of strikingly similar data in their paper independently, and they responded to request that the paper be retracted from International Journal of Oncology. All the authors agreed that the article should be retracted. The Editor apologizes to the readership for any inconvenience caused. ,