LncRNA CASC2 Regulate Cell Proliferation and Invasion by Targeting miR-155/SOCS1 Axis in Hepatocellular Carcinoma

Long noncoding RNAs (lncRNAs) have been reported to be involved in the development and progression of various human malignancies. However, the role of lncRNA CASC2 in hepatocellular carcinoma (HCC) remains mostly unknown. The aim of this study was to investigate the potential roles and underlying mechanisms of CASC2 in HCC progression. We found that CASC2 expressions were downregulated in HCC tissue samples and cell lines. The clinical assays revealed that lower levels of CASC2 were associated with the TNM stage, lymph node metastasis, and a poorer prognosis specific to HCC patients. Overexpression of CASC2 inhibited the proliferating, migratory, and invasion capacity of HCC cells. Bioinformatics analysis and the luciferase reporter assay revealed that CASC2 worked as a molecular sponge for miR-155. And CASC2 could upregulate SOCS1 expression by inhibiting miR-155 expression in HCC cells. Furthermore, SOCS1 inhibition partially inverses the suppression effect of cell proliferation, migration, and invasion regulated by CASC2 in Huh7 and HepG2 cells. Taken together, our findings identified CASC2 as a tumor suppressor to inhibit HCC development by regulating the miR-155/SOCS1 axis, and CASC2 might be a potential therapeutic target of HCC for future clinical treatment.

[1]  Zhiqiang Li,et al.  The lncRNA CASC2 Modulates Hepatocellular Carcinoma Cell Sensitivity and Resistance to TRAIL Through Apoptotic and Non-Apoptotic Signaling , 2022, Frontiers in Oncology.

[2]  C. Qin,et al.  Functional role of miR‑155 in physiological and pathological processes of liver injury (Review). , 2021, Molecular medicine reports.

[3]  Shinn-Ying Ho,et al.  Novel miRNA signature for predicting the stage of hepatocellular carcinoma , 2020, Scientific Reports.

[4]  Juan Yang,et al.  The expression of lncRNA XIST in hepatocellular carcinoma cells and its effect on biological function. , 2020, Journal of B.U.ON. : official journal of the Balkan Union of Oncology.

[5]  Xiaopeng Xu,et al.  miR-155-5p increases the sensitivity of liver cancer cells to adriamycin by regulating ATG5-mediated autophagy. , 2020, Neoplasma (Bratislava).

[6]  Miao Wang,et al.  LncRNA CTBP1-AS2 Promotes Cell Proliferation in Hepatocellular Carcinoma by Regulating miR-623/Cyclin D1 Axis. , 2020, Cancer biotherapy & radiopharmaceuticals.

[7]  F. Piñero,et al.  Biomarkers in Hepatocellular Carcinoma: Diagnosis, Prognosis and Treatment Response Assessment , 2020, Cells.

[8]  M. Taheri,et al.  The role of long non-coding RNA CASC2 in the carcinogenesis process. , 2020, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[9]  Yang-Hsiang Lin Crosstalk of lncRNA and Cellular Metabolism and Their Regulatory Mechanism in Cancer , 2020, International journal of molecular sciences.

[10]  Wei Zhang,et al.  SOCS1 blocks G1-S transition in hepatocellular carcinoma by reducing the stability of the CyclinD1/CDK4 complex in the nucleus , 2020, Aging.

[11]  Z. Hou,et al.  Long Non-coding RNA MALAT1 Promotes Angiogenesis and Immunosuppressive Properties of HCC Cells by sponging miR-140. , 2019, American journal of physiology. Cell physiology.

[12]  Shuwei Chen,et al.  Long noncoding RNA NEAT1 suppresses sorafenib sensitivity of hepatocellular carcinoma cells via regulating miR‐335–c‐Met , 2019, Journal of cellular physiology.

[13]  Ping Chen,et al.  Long non-coding RNA CASC2 enhances berberine-induced cytotoxicity in colorectal cancer cells by silencing BCL2 , 2019, Molecular medicine reports.

[14]  Xiaodong Zhang,et al.  Long non-coding RNA HOTAIR promotes exosome secretion by regulating RAB35 and SNAP23 in hepatocellular carcinoma , 2019, Molecular Cancer.

[15]  W. Zhang,et al.  Long non-coding RNA cancer susceptibility candidate 2 inhibits the cell proliferation, invasion and angiogenesis of cervical cancer through the MAPK pathway. , 2019, European review for medical and pharmacological sciences.

[16]  Haitao Zhao,et al.  Comprehensive analysis of a ceRNA network reveals potential prognostic cytoplasmic lncRNAs involved in HCC progression , 2019, Journal of cellular physiology.

[17]  M. Radwan,et al.  RASSF1A and SOCS1 genes methylation status as a noninvasive marker for hepatocellular carcinoma. , 2019, Cancer biomarkers : section A of Disease markers.

[18]  A. Pillai,et al.  Goals and targets for personalized therapy for HCC , 2019, Hepatology International.

[19]  Bin Zhang,et al.  LncRNA HOTAIR epigenetically suppresses miR-122 expression in hepatocellular carcinoma via DNA methylation , 2018, EBioMedicine.

[20]  M. Ahmadvand,et al.  Over expression of circulating miR-155 predicts prognosis in diffuse large B-cell lymphoma. , 2018, Leukemia research.

[21]  M. Khaniani,et al.  Simultaneous downregulation of miR‐21 and miR‐155 through oleuropein for breast cancer prevention and therapy , 2018, Journal of cellular biochemistry.

[22]  Qian Qian,et al.  SOCS1 is associated with clinical progression and acts as an oncogenic role in triple‐negative breast cancer , 2018, IUBMB life.

[23]  Lixiang Jiang,et al.  Long non-coding RNA CASC2 inhibits tumorigenesis via the miR-181a/PLXNC1 axis in melanoma , 2018, Acta biochimica et biophysica Sinica.

[24]  Zhangli Liu,et al.  Upregulation of CASC2 sensitized glioma to temozolomide cytotoxicity through autophagy inhibition by sponging miR-193a-5p and regulating mTOR expression. , 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[25]  Zeping Han,et al.  Overexpression of Long Non‐Coding RNA MEG3 Inhibits Proliferation of Hepatocellular Carcinoma Huh7 Cells via Negative Modulation of miRNA‐664 , 2017, Journal of cellular biochemistry.

[26]  Xiangjian Chen,et al.  Low expression of long noncoding RNA CASC2 indicates a poor prognosis and promotes tumorigenesis in thyroid carcinoma. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[27]  Dalong Song,et al.  MiR‐155 inhibits proliferation and invasion by directly targeting PDCD4 in non‐small cell lung cancer , 2017, Thoracic cancer.

[28]  Jianfeng Zhou,et al.  Overexpression of long non-coding RNA cancer susceptibility 2 inhibits cell invasion and angiogenesis in gastric cancer , 2017, Molecular medicine reports.

[29]  Meng Xu,et al.  Long non-coding RNA CASC2 suppresses epithelial-mesenchymal transition of hepatocellular carcinoma cells through CASC2/miR-367/FBXW7 axis , 2017, Molecular Cancer.

[30]  Chunhong Hu,et al.  Modulation of CASC2/miR-21/PTEN pathway sensitizes cervical cancer to cisplatin. , 2017, Archives of biochemistry and biophysics.

[31]  A. Ozakyol Global Epidemiology of Hepatocellular Carcinoma (HCC Epidemiology) , 2017, Journal of Gastrointestinal Cancer.

[32]  I. Lossos,et al.  miR-155 regulates HGAL expression and increases lymphoma cell motility. , 2012, Blood.