<p>SNHG8 is upregulated in esophageal squamous cell carcinoma and directly sponges microRNA-411 to increase oncogenicity by upregulating KPNA2</p>
Authors: Jinxia Song
Huali Song
Lianwei Lu
Shoubo Li
Journal: OncoTargets and Therapy (2019)
Discipline: CLINICAL MEDICINE
Keywords: esophageal squamous cell carcinoma; karyopherin alpha 2; microRNA-411; small nucleolar RNA host gene 8.
Affiliations: Department of Gastroenterology, Sunshine Union Hospital, Weifang, Shandong 261061, People's Republic of China., Department of Oncology, Qingdao Eighth People's Hospital, Qingdao, Shandong 266100, People's Republic of China., Department of Imaging, Binhai Hospital, Weifang People's Hospital, Weifang, Shandong 262737, People's Republic of China., Department of Thoracic Surgery, People's Hospital of Weifang Binhai Economic and Technological Development Zone, Weifang, Shandong 262737, People's Republic of China.

Abstract:  Background: The long noncoding RNA, small nucleolar RNA host gene 8 (SNHG8), is upregulated in multiple human cancer types. However, whether SNHG8 is aberrantly expressed in esophageal squamous cell carcinoma (ESCC) and its biological functions have yet to be elucidated. Thus, we aimed to determine the expression status of SNHG8 in ESCC, explore the effects of SNHG8 on the oncogenicity of ESCC, and investigate the potential underlying mechanisms. Methods: SNHG8 expression in ESCC tissues and cell lines was determined via reverse-transcription quantitative polymerase chain reaction. The actions of SNHG8 on the malignant characteristics of ESCC were explored using CCK-8 assay, flow-cytometric analysis, Transwell migration and invasion assays, and tumor xenografts in nude mice. Results: SNHG8 expression was significantly higher in ESCC tissues and cell lines. High SNHG8 expression was revealed to closely correlate with primary tumor invasion depth, lymph node metastases, TNM stage, and worse overall survival among patients with ESCC. Functional investigation showed that ablation of SNHG8 notably restricted ESCC cell proliferation, migration, and invasion while inducing apoptosis in vitro and hindered tumor growth in vivo. In the meantime, SNHG8 acted as a molecular sponge of microRNA-411 (miR-411) in ESCC. Furthermore, miR-411 exerted a tumor-suppressive effect on ESCC cells, and karyopherin alpha 2 (KPNA2) turned out to be a direct target gene of miR-411. Restoring KPNA2 expression neutralized the inhibitory effects of miR-411 overexpression on the malignant behaviors of ESCC cells. Moreover, silencing of miR-411 abrogated the influence of SNHG8 downregulation in ESCC cells. Conclusion: SNHG8 may play oncogenic roles in the malignancy of ESCC by sponging miR-411 to increase KPNA2 expression. The SNHG8-miR-411-KPNA2 pathway may be a novel target for the treatment of patients with ESCC and offer potential biomarkers for the diagnosis and prognosis of ESCC. 

Retracted: Yes

PubPeer comments:
 Fig 8A.  The images of tumor xenografts of nude mice injected with siSNHG8u2013transfected or si-scrambleu2013transfected cells .  What appears to be the same ruler has appeared in studies from a number of institutions. *[left]* Fig 7B from [Cheng et al (2019)] .  A representative image of the [Sw1990] tumors at the end of the experiment . *[right* Fig 7B from [Wang et al (2019)] .  Representative images of [H522] tumor xenografts in the agomir-718 group and agomir-NC group .  Fig 7A from [Xu et al (2020)] .  Representative images of subcutaneous xenografts derived from the agomir-936- or agomir-NC-transfected Y79 cells .  , 
 Figs 2C, 4B, 6C.  Two panels (blue boxes) have different descriptions but are almost identical.  , 
 #2 **Four** flow-cytometry plots share most of their points in common, suggesting that they come from the same raw data file (differently gated and filtered).  Left-hand panel is from Fig 2C of [Wang et al (2020)] . Right-hand panel is from Fig 2C of [Qin et al (2020)] . Here in context:  ----------------------------------------------  There may be other panels in common. , 
 Retracted [4 October 2021] . -------------------------- The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. Concerns were raised over alleged image duplication in Figures 4B and 6C with similar images from unrelated articles, specifically: - Figure 4B panel Eca109 miR-411 mimics and Figure 6C panel TE-1 miR-411 mimics+pcDNA3.1, appear to have been duplicated with similar images in Figure 2C from Wang et al, 2020 and Figure 2C from Qin et al, 2020 . The authors responded to our queries but were unable to provide a satisfactory explanation for the alleged duplication and could not provide satisfactory original data for their study. The Editor advised for the article to be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. , 
 - *[left]* Fig 1H from  LncRNA NOP14-AS1 Promotes Tongue Squamous Cell Carcinoma Progression by Targeting MicroRNA-665 HMGB3 Axis ([Li et al 2021] ). - *[right]* **Fig 7G**.  ,