Long Noncoding RNA FGFR3-AS1 Promotes Hepatocellular Carcinoma Carcinogenesis via Modulating the PI3K/AKT Pathway.

Hepatocellular carcinoma (HCC) as one of the most refractory cancers leads to high mortality worldwide. Long noncoding RNAs have been widely acknowledged as important biomarkers and therapeutic targets in HCC. In this study, we investigated the effects of long noncoding RNA FGFR3-AS1 on tumor growth and metastasis in HCC. First, we found that the expression of FGFR3-AS1 was upregulated about threefold in HCC samples and cell lines. We knocked down FGFR3-AS1 in Huh7 and Hep3B cells and found that FGFR3-AS1 knockdown significantly inhibited cell proliferation but induced apoptosis. Moreover, FGFR3-AS1 knockdown led to more HCC cells arrested in the G0 stage. FGFR3-AS1 knockdown significantly inhibited cell migration and invasion. Additionally, we found that FGFR3-AS1 silencing dramatically delayed tumor growth in vivo. We found that, mechanistically, FGFR3-AS1 silencing decreased the activation of the PI3K/AKT signaling pathway. Taken together, our data demonstrated the pro-oncogenic role of FGFR3-AS1 in HCC and suggested that FGFR3-AS1 may serve as a novel biomarker for the diagnosis and therapeutic target for HCC treatment.

[1]  Hongyan Qu,et al.  lncRNA CCAT1 contributes to the growth and invasion of gastric cancer via targeting miR‐219‐1 , 2019, Journal of cellular biochemistry.

[2]  Yuchen Liu,et al.  Knockdown of long noncoding RNA FGFR3- AS1 induces cell proliferation inhibition, apoptosis and motility reduction in bladder cancer. , 2017, Cancer biomarkers : section A of Disease markers.

[3]  J. Si,et al.  Decreased long non-coding RNA MTM contributes to gastric cancer cell migration and invasion via modulating MT1F , 2017, Oncotarget.

[4]  Ming Xie,et al.  LncRNA BCAR4 promotes colon cancer progression via activating Wnt/β-catenin signaling , 2017, Oncotarget.

[5]  Wen-Ling Chan,et al.  Long noncoding RNA MIAT promotes non-small cell lung cancer proliferation and metastasis through MMP9 activation , 2017, Oncotarget.

[6]  X. Qin,et al.  Diagnosis, prognosis and bioinformatics analysis of lncRNAs in hepatocellular carcinoma , 2017, Oncotarget.

[7]  Jixiang Wu,et al.  LncSHRG promotes hepatocellular carcinoma progression by activating HES6 , 2017, Oncotarget.

[8]  Xiaoming Fan,et al.  The long noncoding RNA TUG1 acts as a competing endogenous RNA to regulate the Hedgehog pathway by targeting miR-132 in hepatocellular carcinoma , 2017, Oncotarget.

[9]  Chenlin Song,et al.  LncRNA-SVUGP2 suppresses progression of hepatocellular carcinoma , 2017, Oncotarget.

[10]  Xiaoli Shen,et al.  DNA methylation signature of long noncoding RNA genes during human pre-implantation embryonic development , 2017, Oncotarget.

[11]  Ying Feng,et al.  Downregulation of serum RAB27B confers improved prognosis and is associated with hepatocellular carcinoma progression through PI3K-AKT-P21 signaling , 2017, Oncotarget.

[12]  S. Tajbakhsh lncRNA-Encoded Polypeptide SPAR(s) with mTORC1 to Regulate Skeletal Muscle Regeneration. , 2017, Cell stem cell.

[13]  Ying Du,et al.  Long noncoding RNA lncKdm2b is required for ILC3 maintenance by initiation of Zfp292 expression , 2017, Nature Immunology.

[14]  Akinobu Matsumoto,et al.  mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide , 2016, Nature.

[15]  P. Anninos,et al.  A combined study of MEG and pico-Tesla TMS on children with autism disorder. , 2016, Journal of integrative neuroscience.

[16]  F. Marra,et al.  Challenges of advanced hepatocellular carcinoma , 2016, World journal of gastroenterology.

[17]  P. Zhu,et al.  LncSox4 promotes the self-renewal of liver tumour-initiating cells through Stat3-mediated Sox4 expression , 2016, Nature Communications.

[18]  Ze-Guang Han,et al.  Functional genomic studies: insights into the pathogenesis of liver cancer. , 2012, Annual review of genomics and human genetics.

[19]  Siwei Zhang,et al.  Liver cancer epidemic in China: past, present and future. , 2011, Seminars in cancer biology.

[20]  E. Farber Pathogenesis of liver cancer. , 1974, Archives of pathology.

[21]  D. Holdstock Past, present--and future? , 2005, Medicine, conflict, and survival.