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Jing Yang,1,2 Kun Li,3 Jian Chen,4 Xiaoxiong Hu,5,6 He Wang,2 Xuan Zhu1 1Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People’s Republic of China; 2Department of Gastroenterology and Hepatology, The People’s Hospital of Yichun City, Yichun 336000, People’s Republic of China; 3Department of General Surgery, The People’s Hospital of Yichun City, Yichun 336000, People’s Republic of China; 4Department of Oncology, The People’s Hospital of Yichun City, Yichun 336000, People’s Republic of China; 5Clinic Research Center of People’s Hospital of Yichun City, Yichun 336000, People’s Republic of China; 6Department of Infection Disease, The People’s Hospital of Yichun City, Yichun 336000, People’s Republic of ChinaCorrespondence: Xuan ZhuDepartment of Gastroenterology, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Road, Donghu District, Nanchang 330006, Jiangxi, People’s Republic of ChinaTel +86-0791-88692748Email jyyfyzx@163.comBackground: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide. LINC00460, a novel long non-coding RNA (lncRNA), was recently confirmed as an oncogene in various cancers. However, the biological function and underlying mechanism of LINC00460 in HCC is largely obscure.Methods: Fifty pairs of tumor tissue and adjacent normal tissues from HCC patients, as well as six HCC cell lines and a normal human hepatic epithelial cell line were subjected to qRT-PCR assay to evaluate the expression levels of LINC00460. CCK-8 assays were used to detect the proliferation of HCC cells. Transwell assay was used to measure the migration and invasion abilities of HCC cells. RNA pull-down and luciferase assays were performed to verify the direct interaction between LINC00460 and miR-342-3p. A xenograft model of HCC was established to validate the in vivo function of LINC00460 in HCC progression.Results: We firstly detected LINC00460 expression was significantly upregulated in both HCC tumor tissues and cell lines. The upregulation of LINC00460 was positively associated with HCC progression. Functionally, LINC00460 facilitated HCC cell proliferation, migration, and invasion capacities, which due to that LINC00460 could physically bind to and repress miR-342-3p to elevate the expression of AGR2.Conclusion: Our data firstly reveal the clinical relevance, biological function, and regulatory mechanism of LINC00460 in HCC development. LINC00460 promotes HCC progression by elevating AGR2 expression via sponging miR-342-3p, providing a promising therapeutic target for HCC treatment.Keywords: hepatocellular carcinoma, LncRNA, LINC00460, miR-342-3p, AGR2, migration, invasion

Fang Wang,1 Shaobo Liang,2 Xiaowei Liu,1 Lei Han,1 Junye Wang,1 Qin Du1 1Department of Oncology, Affiliated Hospital of Jining Medical College, Jining 272029, China; 2Department of Gastroenterology, Central Hospital of Shanxian County, Heze, 274399, China Background: Increasing evidence has shown that long non-coding RNAs (lncRNAs) play important roles in the occurrence and development of human cancers. LINC00460, a novel tumor-related lncRNA, has been reported to be involved in several types of human malignancies. However, the role of LINC00460 in gastric cancer (GC) is still unclear. The present study aimed at exploring the biological role of LINC00460 in GC and illuminating the potential molecular mechanisms. Methods: In this study, qRT-PCR, western blotting, MTT assay, and Transwell invasion assay were used to conduct relevant experimental analysis. Results: Here, we found that LINC00460 was highly expressed in GC tissues and cell lines. Moreover, LINC00460 over-expression was found to promote GC cell proliferation, migration and invasion, whereas LINC00460 down-regulation significantly inhibited these processes. Notably, we confirmed that LINC00460 could up-regulate KDM2A expression by competitively binding to miR-342-3p in GC cells. Furthermore, the suppressive effects of LINC00460 down-regulation on GC cell proliferation, migration and invasion were partially reversed by a miR-342-3p inhibitor. Conclusion: In summary, our findings provide evidence for LINC00460 as a potential therapeutic target in GC. Keywords: LINC00460, KDM2A, miR-342-3p, gastric cancer

Wenpeng Liu,1,* Lei Kang,2,* Juqiang Han,3 Yadong Wang,1 Chuan Shen,1 Zhifeng Yan,4 Yanhong Tai,5 Caiyan Zhao1 1Department of Infectious Diseases, Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China; 2Department of Nuclear Medicine, Peking University First Hospital, Beijing, China; 3Institute of Liver Disease, Beijing Military General Hospital, Beijing, China; 4Department of Gynecology and Obstetrics, PLA General Hospital, Beijing, China; 5Department of Pathology, Hospital of PLA, Beijing, China *These authors contributed equally to this work Background: Insulin-like growth factor-1 receptor (IGF-1R) is a well-studied oncogenic factor that promotes cell proliferation and energy metabolism and is overexpressed in numerous cancers including hepatocellular carcinoma (HCC). Aerobic glycolysis is a hallmark of cancer, and drugs targeting its regulators, including IGF-1R, are being developed. However, the mechanisms of IGF-1R inhibition and the physiological significance of the IGF-1R inhibitors in cancer cells are unclear. Materials and methods: Cell proliferation was evaluated by cell counting Kit-8 and colony formation assay. Western blot and real-time PCR were accordingly used to detect the relevant proteins, miRNA and gene expression. Luciferase reporter assays were used to illustrate the interaction between miR-342-3p and IGF-1R. The effect of miR-342-3p on glycolysis was determined by glucose uptake, ATP concentration, lactate generation, extracellular acidification rate and oxygen consumption rate assays. In vivo, subcutaneous tumor formation assay and PET were performed in nude mice. Results: In this study, we demonstrate that by directly targeting the 3’-UTR (3’-untranslated regions) of IGF-1R, microRNA-342-3p (miR-342-3p) suppresses IGF-1R-mediated PI3K/AKT/GLUT1 signaling pathway both in vitro and in vivo. Through suppression of IGF-1R, miR-342-3p dampens glycolysis by decreasing glucose uptake, lactate generation, ATP production, and extracellular acidification rate (ECAR), and increasing oxygen consumption rate (OCR) in hepatoma cells. Importantly, glycolysis regulated by miR-342-3p is critical for its regulating HCC growth both in vitro and in vivo. Conclusion: Our findings provide clues regarding the role of miR-342-3p as a tumor suppressor in liver cancer mainly through the inhibition of IGF-1R. Targeting IGF-1R by miR-342-3p could be a potential therapeutic strategy in liver cancer. Keywords: miR-342-3p, IGF-1R, liver cancer, glycolysis, metabolism, PET

Wenpeng Liu,1,* Lei Kang,2,* Juqiang Han,3 Yadong Wang,1 Chuan Shen,1 Zhifeng Yan,4 Yanhong Tai,5 Caiyan Zhao1 1Department of Infectious Diseases, Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China; 2Department of Nuclear Medicine, Peking University First Hospital, Beijing, China; 3Institute of Liver Disease, Beijing Military General Hospital, Beijing, China; 4Department of Gynecology and Obstetrics, PLA General Hospital, Beijing, China; 5Department of Pathology, Hospital of PLA, Beijing, China *These authors contributed equally to this work Background: Insulin-like growth factor-1 receptor (IGF-1R) is a well-studied oncogenic factor that promotes cell proliferation and energy metabolism and is overexpressed in numerous cancers including hepatocellular carcinoma (HCC). Aerobic glycolysis is a hallmark of cancer, and drugs targeting its regulators, including IGF-1R, are being developed. However, the mechanisms of IGF-1R inhibition and the physiological significance of the IGF-1R inhibitors in cancer cells are unclear. Materials and methods: Cell proliferation was evaluated by cell counting Kit-8 and colony formation assay. Western blot and real-time PCR were accordingly used to detect the relevant proteins, miRNA and gene expression. Luciferase reporter assays were used to illustrate the interaction between miR-342-3p and IGF-1R. The effect of miR-342-3p on glycolysis was determined by glucose uptake, ATP concentration, lactate generation, extracellular acidification rate and oxygen consumption rate assays. In vivo, subcutaneous tumor formation assay and PET were performed in nude mice. Results: In this study, we demonstrate that by directly targeting the 3’-UTR (3’-untranslated regions) of IGF-1R, microRNA-342-3p (miR-342-3p) suppresses IGF-1R-mediated PI3K/AKT/GLUT1 signaling pathway both in vitro and in vivo. Through suppression of IGF-1R, miR-342-3p dampens glycolysis by decreasing glucose uptake, lactate generation, ATP production, and extracellular acidification rate (ECAR), and increasing oxygen consumption rate (OCR) in hepatoma cells. Importantly, glycolysis regulated by miR-342-3p is critical for its regulating HCC growth both in vitro and in vivo. Conclusion: Our findings provide clues regarding the role of miR-342-3p as a tumor suppressor in liver cancer mainly through the inhibition of IGF-1R. Targeting IGF-1R by miR-342-3p could be a potential therapeutic strategy in liver cancer. Keywords: miR-342-3p, IGF-1R, liver cancer, glycolysis, metabolism, PET

Fang Wang,1 Shaobo Liang,2 Xiaowei Liu,1 Lei Han,1 Junye Wang,1 Qin Du1 1Department of Oncology, Affiliated Hospital of Jining Medical College, Jining 272029, China; 2Department of Gastroenterology, Central Hospital of Shanxian County, Heze, 274399, China Background: Increasing evidence has shown that long non-coding RNAs (lncRNAs) play important roles in the occurrence and development of human cancers. LINC00460, a novel tumor-related lncRNA, has been reported to be involved in several types of human malignancies. However, the role of LINC00460 in gastric cancer (GC) is still unclear. The present study aimed at exploring the biological role of LINC00460 in GC and illuminating the potential molecular mechanisms. Methods: In this study, qRT-PCR, western blotting, MTT assay, and Transwell invasion assay were used to conduct relevant experimental analysis. Results: Here, we found that LINC00460 was highly expressed in GC tissues and cell lines. Moreover, LINC00460 over-expression was found to promote GC cell proliferation, migration and invasion, whereas LINC00460 down-regulation significantly inhibited these processes. Notably, we confirmed that LINC00460 could up-regulate KDM2A expression by competitively binding to miR-342-3p in GC cells. Furthermore, the suppressive effects of LINC00460 down-regulation on GC cell proliferation, migration and invasion were partially reversed by a miR-342-3p inhibitor. Conclusion: In summary, our findings provide evidence for LINC00460 as a potential therapeutic target in GC. Keywords: LINC00460, KDM2A, miR-342-3p, gastric cancer