CircDLST promotes the tumorigenesis and metastasis of gastric cancer by sponging miR-502-5p and activating the NRAS/MEK1/ERK1/2 signaling
Authors: Jing Zhang
Rui Liang
Rui Zhang
Lidan Hou
Xiaoyu Chen
Jinshui Zhu
Wei Chen
Journal: Molecular Cancer (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Gastric cancer; Growth; Metastasis; NRAS; circDLST
Affiliations: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, China. ., Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, China.

Abstract:  Background: Accumulating evidence shows that, the dysregulation of circular RNAs (circRNAs) is associated with the progression of multiple malignancies. But, the underlying mechanisms by which has_circ_0032627 (circDLST) contributed to gastric cancer (GC) remain undocumented. Methods: The expression and cellular localization of circDLST and its association with clinicopathological characteristics and prognosis in patients with GC was analysed by using fluorescence in situ hybridization. Gain- and loss-of-function experiments as well as a subcutaneous xenograft tumor model and a liver metastasis model from orthotopic implantation of GC tissues were conducted to assess the role of circDLST in GC cells. CircDLST specific binding with miR-502-5p was confirmed by dual luciferase gene report, RNA immunoprecipitation (RIP) assays and RIP-miRNA expression profiling. qRT-PCR and Western blot analysis was used to detect the effects of circDLST on miR-502-5p-mediated NRAS/MEK1/ERK1/2 signaling in GC cells. Results: The expression levels of circDLST were dramatically elevated in GC tissues as compared with the adjacent normal tissues, and acted as an independent prognostic factor of poor survival in patients with GC. Knockdown of circDLST inhibited the cell viability, colony formation, DNA synthesis, cell invasion and liver metastasis in vitro and in vivo, whereas overexpression of circDLST had the opposite effects. Furthermore, circDLST was co-localized with miR-502-5p in the cytoplasm of GC cells, and acted as a sponge of miR-502-3p in GC cells, which abrogated the tumor promoting effects of circDLST by inactivating the NRAS/MEK1/ERK1/2 signaling in GC cells. Conclusion: CircDLST promotes the tumorigenesis and metastasis of GC cells by sponging miR-502-5p to activate the NRAS/MEK1/ERK1/2 signaling. 

Retracted: No

PubPeer comments:
 Figure 7 appears to have a duplicate image for different cell lines ![file] , 
 #1 Dear, Thanks for posing such a problem for us and we will check this picture very carefully and repeat this colony formation assay. Best, Jinshui Zhu , 
 According to our experimental data, the two original images appear to have some difference from two gastric cancer cell lines, we will check the two experimental pictures, Sincerely yours! , 
 Correction issued, [12 August 2020] .  Following publication of the original article [1], the authors found an error in Fig. 7d, e. The correct figure is shown below. ![] No acknowledgement to PubPeer or Dendrodoa Grossularia? I am disappoint. , 
 *[left]* Fig 2F. One set of panels earlier appeared, differently labeled, in *[right]* Fig 6C of  Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression ([Zhang et al 2017] ). Could the authors check? ![file] ,