LncRNA HOTAIR epigenetically suppresses miR-122 expression in hepatocellular carcinoma via DNA methylation.

MicroRNA-122 (miR-122), a pivotal liver-specific miRNA, is frequently repressed in hepatocellular carcinoma (HCC) and associated with poor prognosis. Long non-coding RNA (lncRNA) HOTAIR has been proved to function as an oncogene in multiple cancers including HCC. However, the relationship between HOTAIR and miR-122 in HCC remains largely unknown. We investigated the function of HOTAIR and miR-122 in HCC cell models and a xenograft mouse model. The regulatory network between HOTAIR and miR-122 was further detected following overexpression or knockdown of HOTAIR. DNA methylation status of miR-122 promoter region, as well as expression levels of DNMTs, EZH2 and Cyclin G1 were analyzed. In this study, we found that HOTAIR was highly expressed whereas miR-122 was suppressed in HCC, and HOTAIR negatively regulated miR-122 expression in HCC cells. Furthermore, knockdown of HOTAIR dramatically inhibited HCC cell proliferation and induced cell cycle arrest in vitro and suppressed tumorigenicity in vivo by upregulating miR-122 expression. Mechanistically, a CpG island was located in the miR-122 promoter region. HOTAIR epigenetically suppressed miR-122 expression via DNMTs-mediated DNA methylation. Moreover, HOTAIR upregulated DNMTs expression via EZH2. In addition, suppression of miR-122 induced by HOTAIR directly reactivated oncogene Cyclin G1 expression. Collectively, our results suggest that HOTAIR epigenetically suppresses miR-122 expression via DNA methylation, leading to activation of Cyclin G1 and promotion of tumorigenicity in HCC, which provide new insight into the mechanism of HOTAIR-mediated hepatocarcinogenesis via suppressing miR-122.

Cheng D ，Deng J ，Zhang B ，He X ，Meng Z ，Li G ，Ye H ，Zheng S ，Wei L ，Deng X ，Chen R ，Zhou J ... -  《EBioMedicine》

Long noncoding RNA MIR31HG inhibits hepatocellular carcinoma proliferation and metastasis by sponging microRNA-575 to modulate ST7L expression.

Yan S ，Tang Z ，Chen K ，Liu Y ，Yu G ，Chen Q ，Dang H ，Chen F ，Ling J ，Zhu L ，Huang A ，Tang H ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

LncRNA SNHG7 accelerates the proliferation, migration and invasion of hepatocellular carcinoma cells via regulating miR-122-5p and RPL4.

Long noncoding RNAs (lncRNAs) play vital roles in the development and progression of hepatocellular carcinoma (HCC). The recent study finds a strong correlation between lncRNA small nucleolar RNA host gene 7 (SNHG7) and HCC metastasis. However, the molecular mechanism by which SNHG7 regulates HCC progression has not been investigated. In this study, we found that SNHG7 was highly expressed in HCC tissues compared to non-tumor tissues. Data from public databases consistently indicated the up-regulated expression of SNHG7 in HCC. Furthermore, the levels of SNHG7 were up-regulated in four HCC cell lines (Huh7, Hep3B, HCCLM3, MHCC97 H) compared with LO2 cells. Interestingly, the elevated expression of SNHG7 was closely correlated with advanced tumor stages, high tumor grades, vascular invasion and poor prognosis of HCC. Knockdown of SNHG7 markedly inhibited cell proliferation, migration and invasion in HCCLM3 and MHCC97H cells, and prominently suppressed the growth and metastasis of HCCLM3 cells in vivo. Mechanistically, SNHG7 silencing increased the level of miR-122-5p in HCC cells. Luciferase reporter assay revealed the direct interaction between SNHG7 and miR-122-5p. Moreover, SNHG7 knockdown decreased the levels of ribosomal protein L4 (RPL4) mRNA and protein in HCC cells. Accordingly, the stability of RPL4 mRNA was reduced by SNHG7 silencing. More importantly, either miR-122-5p knockdown or RPL4 restoration partially reversed SNHG7 silencing-induced tumor suppressive effects on HCC cells. In conclusion, we demonstrated that SNHG7 expression was up-regulated in HCC. SNHG7 contributed to HCC progression by regulating miR-122-5p and RPL4. Therefore, SNHG7 might be a potential biomarker and therapeutic target for HCC.

Yang X ，Sun L ，Wang L ，Yao B ，Mo H ，Yang W ... -  《-》

Knockdown of LncRNA ANRIL suppresses cell proliferation, metastasis, and invasion via regulating miR-122-5p expression in hepatocellular carcinoma.

Ma J ，Li T ，Han X ，Yuan H ... -  《-》

A novel interplay between HOTAIR and DNA methylation in osteosarcoma cells indicates a new therapeutic strategy.

Li X ，Lu H ，Fan G ，He M ，Sun Y ，Xu K ，Shi F ... -  《-》