Molecular characterization of LASP-1 expression reveals vimentin as its new partner in human hepatocellular carcinoma cells

Salvi, Alessandro; Bongarzone, Italia; Ferrari, Lia; Abeni, Edoardo; Arici, Bruna; Bortoli, Maida De; Scuri, Sabrina; Bonini, Daniela; Grossi, Ilaria; Benetti, Anna; Baiocchi, Gian Luca; Portolani, Nazario; Petro, Giuseppina De

doi:10.3892/ijo.2015.2923

Cited by 32 publications

(44 citation statements)

References 41 publications

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“…XIAP 3′UTR transfected cells expressed lower levels of the epithelial marker (E-cadherin), and higher levels of the mesenchymal marker (Vimentin) as well as LASP1 (Figure 3A, 3C, 3E), a cytoskeletal scaffold protein that plays an important role in cytoskeletal organization and cell migration [23]. These were in consistent with prior research that molecular characterization of LASP1 expression revealed Vimentin as its new partner in human hepatocellular carcinoma cells [24]. Similar results were obtained by qRT-PCR (Figure 3B, 3D, 3F).…”

Section: Resultssupporting

confidence: 89%

XIAP 3′-untranslated region as a ceRNA promotes FSCN1 function in inducing the progression of breast cancer by binding endogenous miR-29a-5p

Zhang

Tao

et al. 2017

Oncotarget

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The non-coding 3′-untranslated region (UTR) of genes play an important role in the regulation of microRNA (miRNA) functions, since it can bind and inactivate multiple miRNAs. Herein, we report that ectopic expression of XIAP 3′UTR increased human breast cancer cells proliferation, colony formation, migration, invasion and xenograft tumor growth and suppressed tumor cell death. To investigate this process, we further correlated the genome-wide transcriptional profiling with the gene expression alterations after transfecting XIAP 3′UTR in MCF-7 cells. We identified a robust, genome-wide mechanism of cell migration, motility and epithelial to mesenchymal transition by which mediated by a previously described cellular component movement factor FSCN1. Expression of XIAP and FSCN1 were up-regulated synergistically after transfecting XIAP 3′UTR in vitro and in vivo. Interactions between XIAP and FSCN1 appear to be a key determinant of these processes. Co-transfection with Dicer siRNA reversed the XIAP 3′UTR-mediated oncogenicity, suggesting the miRNAs might be involved in that process. Furthermore, we demonstrated that one miRNA, miR-29a-5p, can bind to both the XIAP and FSCN1 3′UTRs and play an important role in that interactions. We showed that the 3′UTR of XIAP was able to antagonize miR-29a-5p, and resulted in the increased translation of XIAP and FSCN1. Thus, our findings reveal important new insights into how XIAP 3′UTR works, suggesting that the non-coding XIAP 3′UTR serves as a competitor for miRNA binding and subsequently inactivates miRNA functions, by which XIAP 3′UTR frees the target mRNAs from being repressed.

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Section: Resultssupporting

confidence: 89%

XIAP 3′-untranslated region as a ceRNA promotes FSCN1 function in inducing the progression of breast cancer by binding endogenous miR-29a-5p

Zhang

Tao

et al. 2017

Oncotarget

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“…The LASP1 expression levels are associated with hepatitis B surface antigen and serum α-fetoprotein level of HCC patients. Multivariate survival analysis has also indicated that LASP1 is an independent prognostic factor of patient survival (26,55). Functional assays have demonstrated that LASP1 promotes HCC cell proliferation and migration and yields aggressive phenotypes (26).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-326 inhibits cell proliferation and invasion, activating apoptosis in hepatocellular carcinoma by directly targeting LIM and SH3 protein 1

Ran

Chen

et al. 2017

Oncology Reports

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Hepatocellular carcinoma (HCC) is the fifth-most common cancer and third leading cause of cancer-related deaths worldwide. Increasing evidence indicates that dysregulation of microRNAs is often observed in HCC, and has been extensively investigated in terms of cancer formation, progression, diagnosis, therapy, and prognosis. Recently, microRNA-326 (miR-326) has been demonstrated to play important roles in multiple types of human cancer. However, the expression pattern, clinical significance, roles and regulatory mechanisms of miR-326 in HCC have yet to be elucidated. In this study, miR-326 was frequently downregulated in HCC tissues and cell lines. Low miR-326 expression was significantly associated with the TNM stage, differentiation and lymph node metastasis of HCC patients. Further functional assays demonstrated that the recovered miR-326 expression inhibited HCC cell proliferation and invasion and activated cell apoptosis in vitro. In addition, LIM and SH3 protein 1 (LASP1) was identified as a direct target gene of miR-326 in HCC. Furthermore, LASP1 was upregulated in HCC tissues and cell lines. The expression level of LASP1 mRNA was inversely correlated with that of miR-326 in HCC tissues. Moreover, LASP1 silencing elicited effects similar to miR-326 overexpression on HCC cells, and LASP1 upregulation markedly reversed the effects of miR-326 overexpression on HCC cells. These results revealed that miR-326 suppressed the progression of HCC by directly targeting LASP1. Therefore, miR-326 may be used as a potential therapeutic target for the treatment of patients with HCC.

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“…VIM is a member of intermediate filament protein family involved in cytoskeleton structure regulation associated with physiological and pathological changes [32]. VIM has also been associated with signaling transduction and has been proposed to transfer information from the ECM to the nuclei, which is an important step in the EMT that leads to loss of cellular adhesion and invasion of tumor cells [33].…”

Section: Discussionmentioning

confidence: 99%

Targeted deep sequencing of plasma circulating cell-free DNA reveals Vimentin and Fibulin 1 as potential epigenetic biomarkers for hepatocellular carcinoma

et al. 2017

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Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide, but is still lacking sensitive and specific biomarkers for early diagnosis and prognosis. In this study, we applied targeted massively parallel semiconductor sequencing to assess methylation on a panel of genes (FBLN1, HINT2, LAMC1, LTBP1, LTBP2, PSMA2, PSMA7, PXDN, TGFB1, UBE2L3, VIM and YWHAZ) in plasma circulating cell-free DNA (cfDNA) and to evaluate the potential of these genes as HCC biomarkers in two different series, one from France (42 HCC cases and 42 controls) and one from Thailand (42 HCC cases, 26 chronic liver disease cases and 42 controls). We also analyzed a set of HCC and adjacent tissues and liver cell lines to further compare with ‘The Cancer Genome Atlas’ (TCGA) data. The methylation in cfDNA was detected for FBLN1, PSMA7, PXDN and VIM, with differences in methylation patterns between cases and controls for FBLN1 and VIM. The average methylation level across analyzed CpG-sites was associated with higher odds of HCC for VIM (1.48 [1.02, 2.16] for French cases and 2.18 [1.28, 3.72] for Thai cases), and lower odds of HCC for FBLN1 (0.89 [0.76, 1.03] for French cases and 0.75 [0.63, 0.88] for Thai cases). In conclusion, our study provides evidence that changes in VIM and FBLN1 methylation levels in cfDNA are associated with HCC and could represent useful plasma-based biomarkers. Also, the potential to investigate methylation patterns in cfDNA could bring new strategies for HCC detection and monitoring high-risk groups and response to treatment.

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Molecular characterization of LASP-1 expression reveals vimentin as its new partner in human hepatocellular carcinoma cells

Cited by 32 publications

References 41 publications

XIAP 3′-untranslated region as a ceRNA promotes FSCN1 function in inducing the progression of breast cancer by binding endogenous miR-29a-5p

XIAP 3′-untranslated region as a ceRNA promotes FSCN1 function in inducing the progression of breast cancer by binding endogenous miR-29a-5p

MicroRNA-326 inhibits cell proliferation and invasion, activating apoptosis in hepatocellular carcinoma by directly targeting LIM and SH3 protein 1

Targeted deep sequencing of plasma circulating cell-free DNA reveals Vimentin and Fibulin 1 as potential epigenetic biomarkers for hepatocellular carcinoma

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