Search

The dysregulation of long-chain noncoding ribonucleic acid (lncRNA) is a common phenomenon in many human cancers. Some studies on the biological function of long intergenic non-protein-coding RNA 52 (LINC00052) in cancer indicate that this gene can act as either oncogene or tumor suppressor in some kinds of cancers, such as breast cancer, gastric cancer, liver cancer, and lung cancer. However, the biological function of LINC00052 in colorectal cancer (CRC) has not been studied. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot (WB) techniques were applied to detect the expression levels of LINC00052, miR-574-5p, and calcium-binding and coiled-coil domain 1 (CALCOCO1) in CRC cells and tissues. We authenticated the biological function of LINC00052 and miR-574-5p in CRC, and find some target genes for LINC00052 and miR-574-5p via bioinformatics methods. Dual-luciferase reporter gene assay was performed to identify the interaction between LINC00052 and miR-574-5p or CALCOCO1 and miR-574-5p. The results demonstrated that LINC00052 was downregulated in CRC tissues compared with their adjacent tissues. And LINC00052 could suppress CRC cells metastasis both in vivo and in vitro. Beyond that, miR-574-5p was upregulated in CRC tissues, and as an oncogene, it accelerated CRC cell migration and invasion. More importantly, the results of our research demonstrated that LINC00052 could regulate the expression of CALCOCO1 via sponging miR-574-5p in CRC. Overall, our study illuminated the lncRNA-miRNA functional networks in CRC, and these results might provide a new research direction for the diagnosis and treatment of CRC.

Long non-coding RNAs (lncRNAs) have emerged as critical regulators in a variety of diseases, including many tumors, such as hepatocellular carcinoma (HCC). However, the function and mechanisms responsible for these molecules in HCC are not thoroughly understood. In our previous study, we found that LINC00052 was acted as a tumor suppressor in HCC. In this study, we performed transcription microarray analysis to investigate the target gene of LINC00052, and found that knockdown of LINC00052 significantly increased the expression of SRY-related HMG-box gene 9 (SOX9), which plays an oncogenic role in HCC. Moreover, luciferase reporter assay revealed that LINC00052 promoted miR-101-3p expression by enhancing its promoter activity. In addition, online database analysis tools and luciferase assays showed that miR-101-3p could target SOX9. Quantitative real-time polymerase chain reaction (qRT-PCR) demonstrated that miR-101-3p was downregulated in HCC tissues and HCC cell lines. And we found a positive relationship between LINC00052 and miR-101-3p, and a negative relationship between miR-101-3p and SOX9 in HCC tissues. Besides, miR-101-3p was involved in LINC00052 inhibits HCC cells proliferation and metastasis. At the molecular level, LINC00052 downgulated SOX9 to inhibit HCC cells proliferation and metastasis by interacting with miR-101-3p. It might be a potential application for HCC therapy.

Background/Aims: The long-noncoding RNA colorectal neoplasia differentially expressed (CRNDE) gene was first found to be activated in colorectal neoplasia. Now, it also has been found to be upregulated in many other solid tumors. Whether CRNDE affects tumorigenesis remains unknown. Methods: We conducted bioinformatics, real-time polymerase chain reaction (PCR), Western blot analysis, cell proliferation assay, colony formation assay, wound healing assay, cell migration and invasion assays, RNA immunoprecipitation, and reporter vector construction and luciferase assays. Results: CRNDE was upregulated in hepatocellular carcinoma (HCC). The overexpression of CRNDE promoted HCC cellular proliferation, migration, and invasion in intro and in vivo, and acted as an oncogene in HCC progression. Furthermore, CRNDE impaired miR-136-5P expression in a RISC manner, and a reciprocal repression feedback loop was possible between CRNDE and miR-136-5P. We found that the neighboring mRNA of CRNDE was IRX5, and IRX5 increased the tumorigenicity of HCC cells. IRX5 was a potential downstream target gene of miR-136-5P. MiR-136 regulated IRX5 by interacting with its 3’UTR. In addition, miR-136-5P was involved in the CRNDE-regulated expression of IRX5. Conclusion: CRNDE acted as a tumor oncogene by exhibiting oncogenic properties of human HCC and revealed a novel CRNDE-miR-136-5P-IRX5 regulatory network in HCC. CRNDE may be considered to be a potential target for HCC therapies based on its ability to upregulate IRX5, and it deserves further investigation.

Background Emerging evidences have indicated that long noncoding RNAs (lncRNAs) play essential roles in the development and progression of cancers. Dysregulation of lncRNA MIR31HG has recently been reported in several types of cancers, and researches on the function of MIR31HG in cancers suggested that MIR31HG could act as either oncogene or tumor suppressor. But the functional involvement of MIR31HG has not been studied in hepatocellular carcinoma (HCC). Methods In this study, MTS assays, colony formation assay, Wound-healing assay, Transwell assy, and tumor xenografts experiments were used to identify biological effects of MIR31HG on HCC cells HCC proliferation and metastasis in vitro and in vivo. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to show the interactions of MIR31HG and miR-575. The bioinformatics methods were completed to find the target genes of miR-575. And Dual-luciferase reporter assay and Western blot analysis were further used to confirm the target gene of miR-575. Results We found that overexpression of MIR31HG obviously suppressed HCC proliferation and metastasis in vitro and in vivo, whereas knockdown of MIR31HG had the opposite effects. Besides, overexpression of MIR31HG significantly decreased the expression of microRNA-575 (miR-575), which plays an oncogenic role in HCC. Moreover, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay revealed that MIR31HG exerted tumor-suppressive functions by binding directly to miR-575, and there was a reciprocal inhibition between MIR31HG and miR-575 in the same RNA-induced silencing complex (RISC). Furthermore, overexpression of MIR31HG enhanced the expression of suppression of tumorigenicity 7 like (ST7L), which was identified as a downstream target gene of miR-575. Thus, MIR31HG positively regulated ST7L expression through sponging miR-575, and acted as tumor suppressor in HCC. Conclusions Overall, our study illuminates the role of MIR31HG as a miRNA sponge in HCC, and sheds new light on lncRNA-directed diagnostics and therapeutics in HCC. Electronic supplementary material The online version of this article (10.1186/s13046-018-0853-9) contains supplementary material, which is available to authorized users.

Rap1b was found be dysregulated in several types of cancers. Previously, we have demonstrated that Rap1b affects proliferation, migration and invasion of hepatocellular carcinoma (HCC) cells. However, the definite function of Rap1b in HCC remains unknown. Here, we reported that Rap1b was significantly up-regulated in HCC tissues compared with the non-tumoral liver tissues. Overexpression of Rap1b promoted tumor growth and migration in vitro and tumor formation in vivo. Oppositely, inhibition of Rap1b suppressed the proliferation and migration of HCC cells. Mechanism study revealed that Rap1b could up-regulate Twist 1 expression by enhancing its promoter activity. We concluded that Rap1b increased Twist 1 expression by targeting its promoter activity to induce proliferation and migration of HCC cells.

Various studies revealed that numerous long noncoding RNAs (lncRNAs) have been found dysregulated in HCC and played important role in hepatocarcinogenesis, although the underlying mechanism still remains unclear. Herein, we reported AF119895, a new lncRNA which was identified from microarray and amplified in HCC. Functionally, AF119895 promoted migration and invasion of HCC cells both in vitro and in vivo. Furthermore, we identified that NXF3 was a downstream target of AF119895. NXF3 depletion could decrease HCC cells migration and invasion. In addition, AF119895 could act as an endogenous sponge by binding to miR-6508-3p and reduce miR-6508-3p expression. And miR-6508-3p could regulate NXF3 by interacting with its 3′UTR. These observations collectively demonstrate that AF119895 modulates the repression of NXF3 by binding to miR-6508-3p. Our results outline a novel signaling pathway mediated by AF119895 and suggest its candidacy as a new prognostic biomarker and therapeutic target of HCC.

// Liying Zhu 1, 3, * , Nenghong Yang 4, * , Juan Chen 1 , Tao Zeng 1 , Shaoying Yan 1 , Yuyang Liu 1 , Gangfeng Yu 1 , Qiuxu Chen 1 , Guiqin Du 3 , Wei Pan 3 , Xing Li 3 , Huihao Zhou 1 , Ailong Huang 1, 2 and Hua Tang 1 1 Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China 2 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China 3 Department of Medical Laboratory, Guizhou Medical University, Guiyang, China 4 Department of Hepatobiliary Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, China * These authors have contributed equally to this work Correspondence to: Hua Tang, email: tanghua86162003@cqmu.edu.cn Ailong Huang, email: ahuang1964@163.com Keywords: HCC, LINC00052, EPB41L3, migration, invasion Received: March 22, 2017 Accepted: June 05, 2017 Published: June 29, 2017 ABSTRACT Numerous studies have demonstrated that a class of long noncoding RNAs (lncRNAs) are dysregulated in hepatocellular carcinoma (HCC) and they are closely related with tumorigenesis. Our previous studies indicated that LINC00052 was a downregulated lncRNA in HCC and acted as a tumor suppressor gene. Using transcription microarray analysis, we found that knockdown of LINC00052 resulted in EPB41L3 downregulation. However, the function of EPB41L3 and the mechanism of LINC00052 downregulating EPB41L3 in HCC remain unclear. In this study, we found that overexpression of LINC00052 could upregulate the EPB41L3 expression and it might serve as a tumor suppressor gene in HCC. Database analysis showed that miR-452-5P could target LINC00052. The binding regions between LINC00052 and miR-452-5P were confirmed by luciferase assays. Moreover, LINC00052 inhibited cell malignant behavior by increasing miR-452-5P expression, suggesting that LINC00052 was negatively regulated by miR-452-5P. In addition, overexpression of miR-452-5P resulted in a decrease of EPB41L3 expression, suggesting that EPB41L3 was as a target of miR-452-5P. In conclusion, these results demonstrated that a novel pathway was mediated by LINC00052 in HCC.