Downregulation of Talin1 promotes hepatocellular carcinoma progression through activation of the ERK1/2 pathway

Chen, Peijuan; Lei, Ling; Wang, Jian; Zou, Xiaobao; Zhang, Dongyan; Deng, Ling; Wu, De‐Hua

doi:10.1111/cas.13247

Cited by 27 publications

(16 citation statements)

References 46 publications

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“…On the other side, SRC-1 activates FAK1 [62], which strengthens vinculin, containing focal adhesion complexes [63] that link cells to fibronectin or other components of the ECM [64] and include talin-1 as a hinge between the cytoskeleton and the extracellular space [65]. Downregulation of talin favors activation of the MAPK1/MAPK3 pathway [66].…”

Section: Pi3k/akt/mtor (Pam) Signalingmentioning

confidence: 99%

Simulated Microgravity Influences VEGF, MAPK, and PAM Signaling in Prostate Cancer Cells

Hybel

Dietrichs

Sahana

et al. 2020

IJMS

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Prostate cancer is one of the leading causes of cancer mortality in men worldwide. An unusual but unique environment for studying tumor cell processes is provided by microgravity, either in space or simulated by ground-based devices like a random positioning machine (RPM). In this study, prostate adenocarcinoma-derived PC-3 cells were cultivated on an RPM for time periods of 3 and 5 days. We investigated the genes associated with the cytoskeleton, focal adhesions, extracellular matrix, growth, survival, angiogenesis, and metastasis. The gene expression of signaling factors of the vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK), and PI3K/AKT/mTOR (PAM) pathways was investigated using qPCR. We performed immunofluorescence to study the cytoskeleton, histological staining to examine the morphology, and a time-resolved immunofluorometric assay to analyze the cell culture supernatants. When PC-3 cells were exposed to simulated microgravity (s-µg), some cells remained growing as adherent cells (AD), while most cells detached from the cell culture flask bottom and formed multicellular spheroids (MCS). After 3-day RPM exposure, PC-3 cells revealed significant downregulation of the VEGF, SRC1, AKT, MTOR, and COL1A1 gene expression in MCS, whereas FLT1, RAF1, MEK1, ERK1, FAK1, RICTOR, ACTB, TUBB, and TLN1 mRNAs were not significantly changed. ERK2 and TLN1 were elevated in AD, and FLK1, LAMA3, COL4A5, FN1, VCL, CDH1, and NGAL mRNAs were significantly upregulated in AD and MCS after 3 days. After a 5-day culture in s-µg, the PC-3 cells showed significant downregulations of VEGF mRNA in AD and MCS, and FN1, CDH1, and LAMA3 in AD and SCR1 in MCS. In addition, we measured significant upregulations in FLT1, AKT, ERK1, ERK2, LCN2, COL1A1, TUBB, and VCL mRNAs in AD and MCS, and increases in FLK1, FN1, and COL4A5 in MCS as well as LAMB2, CDH1, RAF1, MEK1, SRC1, and MTOR mRNAs in AD. FAK1 and RICTOR were not altered by s-µg. In parallel, the secretion rate of VEGFA and NGAL proteins decreased. Cytoskeletal alterations (F-actin) were visible, as well as a deposition of collagen in the MCS. In conclusion, RPM-exposure of PC-3 cells induced changes in their morphology, cytoskeleton, and extracellular matrix protein synthesis, as well as in their focal adhesion complex and growth behavior. The significant upregulation of genes belonging to the PAM pathway indicated their involvement in the cellular changes occurring in microgravity.

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Section: Pi3k/akt/mtor (Pam) Signalingmentioning

confidence: 99%

Simulated Microgravity Influences VEGF, MAPK, and PAM Signaling in Prostate Cancer Cells

Hybel

Dietrichs

Sahana

et al. 2020

IJMS

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“…Hepatocellular carcinoma (HCC) is one of the most common malignancies and it is the second most common cause of cancer-related death. As an indicator of cure rates, the median five-year survival rate was approximately 5-9% for HCC [1, 2]. The pathogenesis of HCC is a multistep and multistage process involving environmental factors and genetic factors [3].…”

Section: Introductionmentioning

confidence: 99%

miR-548b-3p Regulates Proliferation, Apoptosis, and Mitochondrial Function by Targeting CIP2A in Hepatocellular Carcinoma

Lin

Wang

2018

BioMed Research International

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The roles of miR-548b-3p in the progression of hepatocellular carcinoma (HCC) remain undiscovered. This study aims to explore the roles and mechanisms of miR-548b-3p in HCC. Using TCGA database, we found that miR-548b-3p expression was lower in HCC compared to the normal tissues, which was further confirmed by RT-qPCR of 20 cases of surgically resected HCC and corresponding normal tissues. miR-548b-3p mimic and inhibitor were transfected into Huh7 and SK-Hep-1 cells, respectively. MTT, colony formation, and cell cycle assays showed that miR-548b-3p mimic suppressed cell growth and G1/S cell cycle transition. In contrast, miR-548b-3p inhibitor facilitated cell growth and cell cycle transition. miR-548b-3p mimic also increased cisplatin sensitivity by upregulating apoptosis rate. JC-1 staining showed that miR-548b-3p mimic downregulated mitochondrial membrane potential, while miR-548b-3p inhibitor showed the opposite effects in SK-Hep-1 cells. Using prediction software, we found that CIP2A was on the target list of miR-548b-3p. miR-548b-3p mimic downregulated CIP2A and its downstream target protein c-Myc. Luciferase reporter assay demonstrated that CIP2A was as a direct target of miR-548b-3p. CIP2A depletion partly reduced the effect of miR-548b-3p mimic/inhibitor on c-Myc. CIP2A depletion also reduced the effect of miR-548b-3p mimic/inhibitor on proliferation. In conclusion, our data demonstrated that miR-548b-3p was downregulated in HCC. miR-548b-3p regulates proliferation, apoptosis and mitochondrial function by targeting CIP2A in HCC.

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“…By the way, TLN1 was correlated with a metastatic phenotype of malignant tumors, such as breast cancer, hepatocellular carcinoma, and prostate cancer. [34][35][36] In glioma, TLN1 had been declared to be highly expressed in bevacizumab-resistant orthotopic xenograft glioma tumor. 37 However, TLN1 expression in glioma cells remained unclear comparing to normal brain cells.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, we might conclude a TIIA/miR-16-5p/TLN1 pathway underlying anti-proliferation, anti-migration and anti-invasion role of TIIA in glioma. By the way, the signaling pathways such as AP-1, integrin, and ERK1/2 signals 35,38,39 behind this axis remained unknown. Taken together, we explored that miR-16-5p upregulation and TLN1 downregulation were accompanied with TIIA treatment in T98 and A172 cells.…”

Section: Discussionmentioning

confidence: 99%

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<p>Tanshinone IIA Suppresses Glioma Cell Proliferation, Migration and Invasion Both in vitro and in vivo Partially Through miR-16-5p/Talin-1 (TLN1) Axis</p>

You¹,

He²,

Wang³

et al. 2020

CMAR

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Background: Tanshinone IIA (TIIA) is one of the active constituents derived from the rhizome of Danshen, a traditional Chinese herbal. Recently, microRNAs (miRNAs) have been suggested to be associated with the anticancer role of TIIA. However, it remains vague of the interaction between miRNAs and TIIA in glioma, a common aggressive brain tumor in humans. Methods: Expression of miRNA (miR)-16-5p and talin-1 (TLN1) was detected using reverse transcription-quantitative polymerase chain reaction and Western blotting. Cell proliferation, migration and invasion were assessed with cell viability assay, transwell assay, Western blotting, and xenograft tumor experiment. The target binding between miR-16-5p and TLN1 was confirmed by dual-luciferase reporter assay and RNA pull-down assay. Results: TIIA treatment inhibited cell viability, migration and invasion, and decreased Cyclin D1, matrix metalloproteinase (MMP)-9 and Vimentin expression in glioma T98G and A172 cells both in vitro and in vivo. Thus, TIIA induced anti-glioma role, wherein miR-16-5p was upregulated and TLN1 was downregulated. Moreover, silencing miR-16-5p could abate TIIA-mediated suppression on glioma cell proliferation, migration and invasion in vitro and in vivo. TLN1 overexpression also exerted tumor-promoting effect in TIIA-treated T98G and A172 cells. Mechanically, miR-16-5p could regulate TLN1 expression via target binding, and depleting TLN1 could counteract the inhibitory effect of miR-16-5p knockdown on the curative effect of TIIA in T98G and A172 cells. Conclusion: TIIA exerted the anti-proliferation, anti-migration and anti-invasion role in glioma cells both in vitro and in vivo partially through regulating miR-16-5p/TLN1 axis.

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Downregulation of Talin1 promotes hepatocellular carcinoma progression through activation of the ERK1/2 pathway

Cited by 27 publications

References 46 publications

Simulated Microgravity Influences VEGF, MAPK, and PAM Signaling in Prostate Cancer Cells

Simulated Microgravity Influences VEGF, MAPK, and PAM Signaling in Prostate Cancer Cells

miR-548b-3p Regulates Proliferation, Apoptosis, and Mitochondrial Function by Targeting CIP2A in Hepatocellular Carcinoma

<p>Tanshinone IIA Suppresses Glioma Cell Proliferation, Migration and Invasion Both in vitro and in vivo Partially Through miR-16-5p/Talin-1 (TLN1) Axis</p>

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