Long non-coding RNA LINC01554 overexpression suppresses viability, migration, and invasion of liver cancer cells through regulating miR-148b-3p/EIF4E3.

Background: Long non-coding RNAs (lncRNAs) can be severed as competing endogenous RNAs (ceRNAs) to regulate target genes or mRNAs via sponging microRNAs (miRNAs). This study explored the effect of LINC01554 on liver cancer cells through the ceRNA mechanism. Methods: Five significantly down-regulated lncRNAs were selected for further verification, and then through bioinformatics, interactive miRNAs and mRNAs of lncRNAs were identified. The relationship between LINC01554, miR-148b-3p and EIF4E3 was detected by the dual luciferase reporter gene assay. Afterwards, HCCLM3 cells were transfected with pCDH-LINC01554, miR-148b-3p inhibitor and miR-148b-3p mimics. Cell viability, apoptosis, migration and invasion were measured by Cell Counting Kit-8, flow cytometer, and Transwell assays. Real-time quantitative PCR (RT-qPCR) and Western blot were used to measure the expressions of related genes and proteins. Results: LINC01554 was significantly down-regulated in the liver cancer cell lines, and was expressed in the cytoplasm of HCCLM3 cells. LINC01554 overexpression inhibited proliferation, migration, and invasion of HCCLM3 cells, and promote their apoptosis (P < 0.05). Besides, LINC01554 overexpression also significantly increased the levels of BAX, BCL2/BAX, P53, cleaved-Caspase3, TIMP3, E-cadherin and EIF4E3 (P < 0.05). Through bioinformatics and dual-luciferase reporter gene assay, LINC01554, miR-148b-3p and EIF4E3 were proved to interact with each other. Furthermore, the effects of miR-148b-3p knockdown on HCCLM3 cells were similar with those of LINC01554 overexpression, and miR-148b-3p mimics could reverse the changes of cell viability, apoptosis, migration, and invasion induced by LINC01554 overexpression. Conclusions: LINC01554 overexpression could suppress the growth and metastasis of HCCLM3 cells via miR-148b-3p/EIF4E3.

Deciphering Role of lncRNA 91H in Liver Cancer: Impact on Tumorigenesis.

OBJECTIVE: This study aimed to investigate functional role of long ncRNA (lncRNA) 91H in liver cancer tumorigenesis, focusing on its effect on cell proliferation, apoptosis, cell cycle progression, migration, invasion, epithelial-mesenchymal transition (EMT) and In vivo tumor growth. MATERIALS AND METHODS: In this experimental study, liver cancer tissues and cell lines were analyzed for lncRNA 91H expression using quantitative reverse transcription polymerase chain reaction (qRT-PCR). By employing si-RNA to silence 91H, we aimed to gain a more in-depth understanding of its specific contributions and effects within these cells. Cell proliferation was assessed through the CCK-8 assay, while apoptosis and cell cycle progression were quantified using Annexin V-FITC staining and flow cytometry, respectively. Migration and invasion capabilities of liver cancer cells were assessed through transwell assay. EMT was assessed by analyzing protein expression levels of EMT-associated markers through western blotting. In vivo effect of 91H was assessed through xenograft experiments. RESULTS: Significantly higher levels of lncRNA 91H were observed in the liver cancer tissues and cell lines, than the normal cells. Silencing 91H in liver cancer cells led to a notable reduction of cell proliferation by inducing apoptosis and arresting the cell cycle. Liver cancer cells with decreased 91H expression exhibited diminished migration and invasion abilities, suggesting a role for 91H in promoting these processes. Furthermore, 91H knockdown weakened EMT in liver cancer cells, indicating its involvement in modulating this critical cellular transition. Furthermore, growth of subcutaneous xenograft tumors and weight was effectively suppressed by sh-lncRNA 91H. CONCLUSION: Our study strongly supports lncRNA 91H's role in liver cancer progression by enhancing proliferation, migration, invasion, and EMT. Targeting 91H reduced in vivo tumor growth, highlighting its potential as a therapeutic liver cancer target. These findings suggest 91H's pivotal role in liver cancer aggressiveness, opening doors for future therapeutic approaches.

Comprehensive analysis of a TPX2-related TRHDE-AS1/PKIA ceRNA network involving prognostic signatures in Hepatitis B virus-infected hepatocellular carcinoma.

Hepatitis B virus (HBV) infection is a main carcinogenic factor of hepatocellular carcinoma (HCC). TPX2 microtubule nucleation factor is recently recommended as a novel prognostic biomarker in HBV-infected HCC tissues. This study aimed to explore a TPX2-related ceRNA regulatory network in HBV-infected HCC and the potential impact on HCC prognosis. We comprehensively identified 541 differential expressed lncRNAs (DElncRNAs), 37 DEmiRNAs and 439 DEmRNAs from HBV-related TCGA-HCC cohorts in TPX2low and TPX2high groups. Based on their RNA-RNA interaction and expression analysis, four DElncRNAs (TRHDE-AS1, DLX6-AS1, SNHG14, HOXA11-AS), four DEmiRNAs (miR-23b, miR-320a, miR-589, miR-126) and five DEmRNAs (PKIA, PCDHA2, SHCBP1, PRSS16, KIF18A) in HCC tumor vs normal groups were subjected to the hub regulatory networks analysis and further prognostic value analysis. Importantly, the TRHDE-AS1/miR-23b/PKIA ceRNA network was associated with HCC prognosis. Furthermore, cellular location analysis and base-base interaction analysis indicated that the cytoplasmic lncRNA TRHDE-AS1 was regarded as a ceRNA to sponging miR-23b and then regulating PKIA. Interestingly, correlation analysis suggested the expression correlation between TRHDE-AS1 and PKIA in HCC. Finally, we further performed the methylation and immune infiltration analysis to explore the functional process of PKIA in HCC. We proposed a ceRNA regulatory network may help elucidate the mechanism by which TPX2 contributes to the prognosis of HBV-related HCC.

Aberrant expression of PI3K/AKT signaling is involved in apoptosis resistance of hepatocellular carcinoma.

Phosphatidylinositol 3-kinase (PI3K)/AKT signaling is a crucial pathway for cell survival and proliferation, which are regulated by several growth factors and activated receptors. Upregulated PI3K/AKT signaling molecules were reported in several cancers and they are associated with altered cellular functions, leading to oncogenesis. Here, we have examined the implications of elevated PI3K/AKT expression in the apoptosis resistance of human hepatocellular carcinoma (HCC) Huh7 cells. We showed that PI3K/AKT signaling is significantly upregulated in Huh7 cells by quantitative polymerase chain reaction and protein expression analysis. Also, perversely upregulated PI3K/AKT signaling Huh7 cells are highly resistant to treatment with chemotherapy drugs (docetaxel and sorafenib) and acquired apoptosis resistance through downregulation of tumor suppressor protein PTEN (phosphatase and tensin homolog deleted on chromosome ten). Hence, we have investigated the effect of PTEN overexpression on apoptosis induction in Huh7 cells. We showed that PTEN overexpressed Huh7 cells became more sensitive toward the aforesaid drugs and induced apoptotic cell death due to intracellular reactive oxygen species (ROS) generation. Concurrently, the overexpression of PTEN leads to the activation of mitochondria facilitated intrinsic apoptosis, evidenced by upregulated cytochrome C, caspase 3, and caspase 9. Collectively, our data suggest that the aberrant expression of PI3K/AKT signaling contributes to apoptosis resistance in HCC.