LncRNA KTN1-AS1 promotes tumor growth of hepatocellular carcinoma by targeting miR-23c/ERBB2IP axis.

Long non-coding RNAs (lncRNAs) are critical regulators in the tumorigenesis and metastasis of hepatocellular carcinoma (HCC). LncRNA KTN1 antisense RNA 1 (KTN1-AS1) has been reported to play an important role in colorectal cancer and correlates with unfavorable clinical outcomes of head and neck squamous cell carcinoma. However, the clinical significance and functional role of KTN1-AS1 in HCC are still unclear. Here, we found that KTN1-AS1 was a highly expressed lncRNA in HCC according to public available databases and our HCC cohort. Further analyses revealed that higher expression of KTN1-AS1 was observed in HCC tissues with large tumor size, high tumor grade and advanced TNM stage. Analysis of survival data indicated that high KTN1-AS1 expression was prominently correlated with poor clinical outcomes of HCC patients. Functionally, KTN1-AS1 knockdown suppressed cell proliferation and colony formation, and increased apoptosis of SMMC-7721 cells in vitro. Furthermore, silencing of KTN1-AS1 restrained tumor growth of HCC in vivo. Conversely, forced expression of KTN1-AS1 facilitated Huh7 cell proliferation and inhibited apoptosis. Mechanistically, KTN1-AS1 inversely regulated miR-23c abundance in HCC cells. Further evidence supported that KTN1-AS1 acted as a competing endogenous RNA (ceRNA) by directly sponging miR-23c in HCC cells. Interestingly, erbb2 interacting protein (ERBB2IP), a known target of miR-23c, was positively regulated by KTN1-AS1 and its restoration reversed KTN1-AS1 knockdown attenuated HCC cell growth. To conclude, our study sheds light on the novel function and underlying mechanism of KTN1-AS1 in HCC, which may accelerate the development of cancer therapy.

Zhang L ，Wang L ，Wang Y ，Chen T ，Liu R ，Yang W ，Liu Q ，Tu K ... -  《-》

miR-23c suppresses tumor growth of human hepatocellular carcinoma by attenuating ERBB2IP.

MicroRNAs (miRNAs) regulate a variety of development and physiologic processes, and play prominent roles in the initiation and progression of human cancers including hepatocellular carcinoma (HCC). MiR-23c is recently emerging as a cancer-associated miRNA, while its expression status and functional role in HCC are unrevealed yet. Here, we found that miR-23c underexpression was associated with the tumorigenesis of HCC based on TCGA data. qRT-PCR analysis revealed that miR-23c expression was reduced in HCC tissues and cell lines. Clinical analysis indicated that low miR-23c expression was correlated with large tumor size, high tumor grade, advanced tumor stage and poor survival of HCC patients. Our in vitro experiments found that overexpression of miR-23c inhibited cell proliferation and induced apoptosis of HCC cells. While miR-23c knockdown led to HCC cell growth arrest and apoptosis. Additionally, miR-23c overexpression repressed tumor growth of HCC in vivo. Mechanistically, erbb2 interacting protein (ERBB2IP) was identified as a direct target of miR-23c in HCC cells. miR-23c suppressed ERBB2IP expression in HCC cells and inversely correlated with ERBB2IP mRNA expression in HCC tissues. Notably, ERBB2IP silencing restrained HCC cell proliferation and induced apoptosis. ERBB2IP restoration reversed the inhibitory effects of miR-23c on HCC cell growth. In conclusion, our observations suggested that miR-23c inhibited cell proliferation and accelerated apoptosis by attenuating ERBB2IP. Targeting miR-23c might open a new avenue for HCC treatment.

Zhang L ，Wang Y ，Wang L ，Yin G ，Li W ，Xian Y ，Yang W ，Liu Q ... -  《-》

A novel lncRNA MCM3AP-AS1 promotes the growth of hepatocellular carcinoma by targeting miR-194-5p/FOXA1 axis.

Wang Y ，Yang L ，Chen T ，Liu X ，Guo Y ，Zhu Q ，Tong X ，Yang W ，Xu Q ，Huang D ，Tu K ... -  《Molecular Cancer》

LncRNA ZEB1-AS1 regulates hepatocellular carcinoma progression by targeting miR-23c.

Xue S ，Lu F ，Sun C ，Zhao J ，Zhen H ，Li X ... -  《World Journal of Surgical Oncology》

LncRNA DBH-AS1 facilitates the tumorigenesis of hepatocellular carcinoma by targeting miR-138 via FAK/Src/ERK pathway.

It has been reported that dysregulated lncRNAs are associated with the pathogenesis of human tumors including hepatocellular carcinoma (HCC). LncRNA DBH-AS1 was reported to be an oncogene in HCC. However, the molecular mechanisms of DBH-AS1 in HCC progression are largely undefined. The expressions of DBH-AS1 and miR-138 in HCC tissues and cells were examined by qRT-PCR. The effects of DBH-AS1 and miR-138 on cell viability, colony formation, apoptosis, and FAK/Src/ERK signaling pathway were determined by CCK-8, colony formation, flow cytometry, and western blot analyses, respectively. Luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to explore the interaction between miR-138 and DBH-AS1. Tumor xenograft assay was performed to confirm the function and mechanism of DBH-AS1 in the progression of HCC in vivo. DBH-AS1 expression was upregulated and miR-138 expression was downregulated in HCC tissues and cells. DBH-AS1 silencing and miR-138 overexpression reduced cell viability, inhibited colony formation, and induced apoptosis. Moreover, DBH-AS1 acted as a molecular sponge of miR-138 to downregulate miR-138 expression. Also, DBH-AS1 overexpression attenuated miR-138-mediated anti-proliferation and pro-apoptosis effects. Additionally, miR-138 overexpression gave rise to a blockage on FAK/Src/ERK pathway, while this effect was undermined by increased DBH-AS1. Furthermore, DBH-AS1 promoted tumor growth and induced the activation of FAK/Src/ERK pathway by targeting miR-138 in vivo. DBH-AS1 facilitated the development of HCC via miR-138/FAK/Src/ERK pathway, establishing the molecular basis of DBH-AS1 in clinical application for HCC.

Bao J ，Chen X ，Hou Y ，Kang G ，Li Q ，Xu Y ... -  《-》