机构：[1]Hongqiao International Research Institution, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[2]Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, the Second Military Medical University, Shanghai, China[3]Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Shanghai, China[4]Department of Cardiology, Tong Ren Hospital, Shanghai Jiao Tong University of Medicine, Shanghai, China[5]Department of Hematology, Tong Ren Hospital, Shanghai Jiao Tong University of Medicine, Shanghai, China
In China, gastric cancer (GC) ranks first in the incidence of all malignant tumors. With high recurrence and distant metastasis, GC has caused considerable mortalities. LncRNA long intergenic non-protein-coding RNA 668 (LINC00668) has been reported to be upregulated in GC cells and predict poor prognosis of GC patients. However, the mechanism of LINC00668 has not been fully investigated in GC. This study aimed to investigate the role of LINC00668 in GC. We found that LINC00668 level was upregulated in GC tissue and cells and predicted poor prognosis. Functionally, LINC00668 knockdown suppressed GC cell migration and invasion. Additionally, LINC00668 knockdown inhibited epithelial to mesenchymal transition (EMT) process. PKN2 exerts similar effects with LINC00668 in GC cells. LINC00668 knockdown suppressed tumor growth and metastasis in vivo. Mechanistically, HuR was predicted to bind with LINC00668 and protein kinase N2 (PKN2). RNA pull-down assays validated the binding between HuR and LINC00668 (or PKN2). Moreover, either silencing of LINC00668 or HuR could decrease PKN2 mRNA stability or reduce PKN2 mRNA and protein levels. Furthermore, PKN2 expression was positively correlated with LINC00668 expression and HuR expression in GC tissues, and HuR expression was positively associated with LINC00668 expression in GC tissues. Finally, rescue assays confirmed that the suppressive effect of LINC00668 silencing on cell migration, invasion, and EMT process was reversed by PKN2 overexpression or HuR upregulation. In conclusion, LINC00668 cooperated with HuR-dependent upregulation of PKN2 to facilitate gastric cancer metastasis, which may provide a potential novel insight for GC treatment.
基金：
Science and Technology Support Project of Chinese and Western Medicine [19401930600]; Scientific Research Project of Shanghai Health and Family Planning Commission [201840023]; General Project of TCM Scientific Research Subject of Shanghai Health and Family Planning Commission [2018LP032]; Coronary Microvascular Disease Innovation Fund [2018-CCACMVD-07]
第一作者机构：[1]Hongqiao International Research Institution, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[2]Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, the Second Military Medical University, Shanghai, China
通讯作者：
通讯机构：[2]Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, the Second Military Medical University, Shanghai, China[3]Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Shanghai, China[*1]Eastern Hepatobiliary Surgery Hospital, No. 225 Changhai Road, Yangpu District, Shanghai, China.
推荐引用方式(GB/T 7714)：
Li Jutang,Dong Wei,Jiang Qixia,et al.LINC00668 cooperated with HuR dependent upregulation of PKN2 to facilitate gastric cancer metastasis[J].CANCER BIOLOGY & THERAPY.2021,22(4):311-323.doi:10.1080/15384047.2021.1905138.
APA：
Li, Jutang,Dong, Wei,Jiang, Qixia,Zhang, Fenglian&Dong, Hui.(2021).LINC00668 cooperated with HuR dependent upregulation of PKN2 to facilitate gastric cancer metastasis.CANCER BIOLOGY & THERAPY,22,(4)
MLA：
Li, Jutang,et al."LINC00668 cooperated with HuR dependent upregulation of PKN2 to facilitate gastric cancer metastasis".CANCER BIOLOGY & THERAPY 22..4(2021):311-323
