Hepatocellular carcinoma (HCC) is a symptomatic disease involed multi-stage program. Here, we elucidated the molecular mechanism of LncTUG1 in the regulation of HCC evolvement. And that may in all likelyhood supply a innovative latent target for HCC’s diagnoses and prognosis. LncRNA TUG1, miR-144-3p, RRAGD and mTOR signaling pathway were screened as target genes in the database, and their expression levels at the cytological level were verified utilized qRT-PCR, Western Blot and immunohistochemistry. Then, we adopted CCK-8, Transwell and flow cytometry assays to estimate cell proliferation, invasion and apoptosis. By use of luciferase reporter assay, the relationships of LncRNA TUG1, miR-144-3p and RRAGD was confirmed. In addition, the LncRNA TUG1-miR-144-3p-RRAGD-mTOR signaling pathway in HCC cells was verified adopted rescue experiment and confirmed by xenotransplantation animal experiment. LncTUG1 in HCC tissues from three databases were identified and further verified through qRT-PCR in HCC cells (Huh7, Hep3B). Knockdown the LncTUG1 could increase apoptosis and inhibite invasion and proliferation in HCC cells. Using inhibitors and activators of the mTOR/S6K pathway, LncTUG1 was confirmed to regulate HCC progression by the mTOR/S6K pathway. Luciferase reporter assay demonstrated that TUG1 negatively regulates miR-144-3p. Furthermore, miR-144-3p negativly regulates RRAGD by way of interacting with the 3′UTR of the RRAGD mRNA in HCC utilized luciferase reporter assay. In vivo, we also discovered that neoplasm weight and tumor volume reduced significantly in subcutaneous xenograft nude mouse models derived from sh-LncTUG1-expressing Huh7 cells. And the expressions of p-mTOR, p-S6K and RRAGD were decreased obviously while the miR144-3p increased in subcutaneous xenograft nude mouse models. In a word, the research suggests that LncTUG1 targets miR-144-3p while miR-144-3p binds to RRAGD mRNA, which induces mTOR/S6K pathway activation and promotes the progression of HCC.

Aims. In this report, it was investigated that hepatoma cells can cause downregulation of cytotoxic T lymphocyte (CTL) function and tea polyphenols (TPs) can reverse downregulation of CTL function. Methods. The expression of GRP78, PD-1, and TIM-3 was detected by western blotting in CTLL-2 cocultured with Hepa1-6 cells. Moreover, perforin (PRF1) and granzyme B (GzmB) protein levels and ER morphology were examined by ELISA and TEM, respectively. After 4-phenylbutyric acid (4-PBA) or tunicamycin (TM) treatment, programmed cell death protein 1 (PD-1), and mucin domain 3 (TIM-3), PRF1, and GzmB were measured by western blotting and ELISA. After sh-CHOP or GSK2656157 (PERK inhibitor) stimulation, the activation of the PERK-CHOP pathway was detected in CTLL-2 cells. Finally, changes in PD-1, TIM-3, PRF1, and GzmB levels were detected to verify the reversal of CTL depletion by TP. Results. The expression of GRP78, PD-1, and TIM-3 clearly increased, and swelling was observed for the endoplasmic reticulum (ER) in CTLL-2 cells cocultured with hepatoma cells. Concurrently, the levels of PRF1 and GzmB decreased. CTLL-2 depletion was induced after stimulation with TM and differed from 4-PBA stimulation. Treatment with sh-CHOP or GSK2656157 caused a decrease in PD-1 and TIM-3 expression, whereas the expression of PRF1 and GzmB clearly increased. After adding TP, the function of CTLs increased markedly. Conclusion. Hepatoma cells induced the depletion of CTLs through the ER stress PERK-CHOP pathway, and TP reversed this depletion by downregulating ER stress.

Background: Hepatocellular carcinoma (HCC) is a symptomatic disease involed multi-stage program. Here, we elucidated the molecular mechanism of LncTUG1 in the regulation of HCC evolvement. And that may in all likelyhood supply a innovative latent target for HCC’s diagnoses and prognosis. Methods: LncRNA TUG1, miR-144-3p, RRAGD and mTOR signaling pathway were screened as target genes in the database, and their expression levels at the cytological level were verified utilized qRT-PCR, Western Blot and immunohistochemistry. Then, we adopted CCK-8, Transwell and flow cytometry assays to estimate cell proliferation, invasion and apoptosis. By use of luciferase reporter assay, the relationships of LncRNA TUG1, miR-144-3p and RRAGD was confirmed. In addition, the LncRNA TUG1-miR-144-3p-RRAGD-mTOR signaling pathway in HCC cells was verified adopted rescue experiment and confirmed by xenotransplantation animal experiment Results: LncTUG1 in HCC tissues from three databases were identified and further verified through qRT-PCR in HCC cells (Huh7, Hep3B). Knockdown the LncTUG1 could increase apoptosis and inhibite invasion and proliferation in HCC cells. Using inhibitors and activators of the mTOR/S6K pathway, LncTUG1 was confirmed to regulate HCC progression by the mTOR/S6K pathway. Luciferase reporter assay demonstrated that TUG1 negatively regulates miR-144-3p. Furthermore, miR-144-3p negativly regulates RRAGD by way of interacting with the 3’UTR of the RRAGD mRNA in HCC utilized luciferase reporter assay. In vivo, we also discovered that neoplasm weight and tumor volume reduced significantly in subcutaneous xenograft nude mouse models derived from sh-LncTUG1-expressing Huh7 cells. And the expressions of p-mTOR, p-S6K and RRAGD were decreased obviously while the miR144-3p increased in subcutaneous xenograft nude mouse models. Conclusion: In a word, the research suggests that LncTUG1 targets miR-144-3p while miR-144-3p binds to RRAGD mRNA, which induces mTOR/S6K pathway activation and promotes the progression of HCC.

Background Hepatocellular carcinoma (HCC) is a symptomatic disease involed multi-stage program. Here, we elucidated the molecular mechanism of LncTUG1 in the regulation of HCC evolvement. And that may in all likelyhood supply a innovative latent target for HCC’s diagnoses and prognosis. Methods LncRNA TUG1, miR-144-3p, RRAGD and mTOR signaling pathway were screened as target genes in the database, and their expression levels at the cytological level were verified utilized qRT-PCR, Western Blot and immunohistochemistry. Then, we adopted CCK-8, Transwell and flow cytometry assays to estimate cell proliferation, invasion and apoptosis. By use of luciferase reporter assay, the relationships of LncRNA TUG1, miR-144-3p and RRAGD was confirmed. In addition, the LncRNA TUG1-miR-144-3p-RRAGD-mTOR signaling pathway in HCC cells was verified adopted rescue experiment and confirmed by xenotransplantation animal experiment Results LncTUG1 in HCC tissues from three databases were identified and further verified through qRT-PCR in HCC cells (Huh7, Hep3B). Knockdown the LncTUG1 could increase apoptosis and inhibite invasion and proliferation in HCC cells. Using inhibitors and activators of the mTOR/S6K pathway, LncTUG1 was confirmed to regulate HCC progression by the mTOR/S6K pathway. Luciferase reporter assay demonstrated that TUG1 negatively regulates miR-144-3p. Furthermore, miR-144-3p negativly regulates RRAGD by way of interacting with the 3’UTR of the RRAGD mRNA in HCC utilized luciferase reporter assay. In vivo, we also discovered that neoplasm weight and tumor volume reduced significantly in subcutaneous xenograft nude mouse models derived from sh-LncTUG1-expressing Huh7 cells. And the expressions of p-mTOR, p-S6K and RRAGD were decreased obviously while the miR144-3p increased in subcutaneous xenograft nude mouse models. Conclusions In a word, the research suggests that LncTUG1 targets miR-144-3p while miR-144-3p binds to RRAGD mRNA, which induces mTOR/S6K pathway activation and promotes the progression of HCC.