Abnormal expression of long non-coding RNA often contributes to unrestricted growth of cancer cells. Long non-coding RNA XIST expression is upregulated in several cancers; however, its modulatory mechanisms have not been reported in hepatocellular carcinoma. In this study, we found that XIST expression was significantly increased in hepatocellular carcinoma tissues and cell lines. XIST promoted cell cycle progression from the G1 phase to the S phase and protected cells from apoptosis, which contributed to hepatocellular carcinoma cell growth. In addition, we revealed that there was reciprocal repression between XIST and miR-139-5p. PDK1 was identified as a direct target of miR-139-5p. We proposed that XIST was responsible for hepatocellular carcinoma cell proliferation, and XIST exerted its function through the miR-139-5p/PDK1 axis.

BackgroundThe long non-coding RNAs (lncRNAs) have participated in the promotion of hepatocellular carcinoma (HCC) initiation and progression. Nevertheless, the biological role and underlying mechanism of LINC01287 in HCC has never been reported.MethodsThe TGCA database was used to explore the abnormal expression of lncRNAs in HCC. Real-time PCR and in situ hybridization assays were used to examine the expression of LINC01287 in HCC tissues. The clinicopathological characteristics of HCC patients in relation to LINC01287 expression were then analyzed. Infection of cells with the si-LINC01287 lentiviral vector was performed to down-regulate LINC01287 expression in HCC cells. MTT and colony formation assays were performed to examine cell growth ability, and FACS analysis was performed to examine the cell cycle and apoptosis. A Boyden assay was used to examine HCC cell invasion ability, and RNA immunoprecipitation tested the interaction between LINC01287 and miR-298. A luciferase reporter assay was used to examine whether STAT3 was a direct target of miR-298, and chromatin immunoprecipitation (ChIP) was used to examine the potential binding of c-jun to the miR-298 promoter.ResultsWe revealed that the expression of LINC01287 was increased in HCC cell lines, as well as tissues. Knockdown of LINC01287 decreased HCC cell growth and invasion both in vitro and in vivo. LINC01287 can negatively regulate miR-298 expression by acting as a ceRNA. miR-298 directly targeted STAT3 and inhibited its expression. LINC01287 exerted its function via the miR-298/STAT3 axis in HCC. Interestingly, STAT3 elevated LINC01287 expression via c-jun, which bound to the LINC01287 promoter. A feedback loop was also discovered between LINC01287 and the miR-298/STAT3 axis.ConclusionsOur data indicated that LINC01287 played an oncogenic role in HCC growth and metastasis and that this lncRNA might serve as a novel molecular target for the treatment of HCC.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0831-2) contains supplementary material, which is available to authorized users.

No abstract

Recently, it was reported that long non‐coding RNAs (lncRNAs) participated in promoting hepatocellular carcinoma (HCC) initiation and progression. Herein, we reported that the expression level of LINC01287 was elevated in HCC cell lines and tissues. LINC01287 down‐regulation inhibited HCC cells growth and invasion both in vitro and in vivo. LINC01287 exerted as a ceRNA and negatively regulated miR‐298 expression. MYB was identified as a downstream target of miR‐298. The miR‐298/MYB axis mediated LINC01287's effect on HCC. To the best of our knowledge, our findings provided the first evidence that LINC01287 functioned as an oncogene in HCC. LINC01287 may be a candidate prognostic biomarker and a target for new therapies in HCC patients.

Pancreatic cancer is one of the major malignancies and causes of mortality worldwide. E3 ubiquitin–protein ligases transfer activated ubiquitin from ubiquitin-conjugating enzymes to protein substrates and confer substrate specificity in cancer. In this study, we first downloaded data from The Cancer Genome Atlas pancreatic adenocarcinoma dataset, acquired all 27 differentially expressed genes (DEGs), and identified genomic alterations. Then, the prognostic significance of DEGs was analyzed, and eight DEGs (MECOM, CBLC, MARCHF4, RNF166, TRIM46, LONRF3, RNF39, and RNF223) and two clinical parameters (pathological N stage and T stage) exhibited prognostic significance. RNF223 showed independent significance as an unfavorable prognostic marker and was chosen for subsequent analysis. Next, the function of RNF223 in the pancreatic cancer cell lines ASPC-1 and PANC-1 was investigated, and RNF223 silencing promoted pancreatic cancer growth and migration. To explore the potential targets and pathways of RNF223 in pancreatic cancer, quantitative proteomics was applied to analyze differentially expressed proteins, and metabolism-related pathways were primarily enriched. Finally, the reason for the elevated expression of RNF223 was analyzed, and KLF4 was shown to contribute to the increased expression of RNF233. In conclusion, this study comprehensively analyzed the clinical significance of E3 ligases. Functional assays revealed that RNF223 promotes cancer by regulating cell metabolism. Finally, the elevated expression of RNF223 was attributed to KLF4-mediated transcriptional activation. This study broadens our knowledge regarding E3 ubiquitin ligases and signal transduction and provides novel markers and therapeutic targets in pancreatic cancer.