scholarly journals Changes in Biomechanical Properties of A375 Cells Due to the Silencing of TMSB4X Expression Are Not Directly Correlated with Alterations in Their Stemness Features

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 769
Author(s):  
Aleksandra Makowiecka ◽  
Ewa Mazurkiewicz ◽  
Ewa Mrówczyńska ◽  
Natalia Malek ◽  
Alice Battistella ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Cell Movement ◽  
Biomechanical Properties ◽  
Soft Agar ◽  
Tumor Formation ◽  
Intermediate Filament Proteins ◽  
Mesenchymal Transition ◽  
Multiple Processes ◽  
A375 Cells

Thymosin β4 (Tβ4) is a small, 44-amino acid polypeptide. It has been implicated in multiple processes, including cell movement, angiogenesis, and stemness. Previously, we reported that melanoma cell lines differ in Tβ4 levels. Studies on stable clones with silenced TMSB4X expression showed that Tβ4 impacted adhesion and epithelial-mesenchymal transition progression. Here, we show that the cells with silenced TMSB4X expression exhibited altered actin cytoskeleton’s organization and subcellular relocalization of two intermediate filament proteins: Nestin and Vimentin. The rearrangement of the cell cytoskeleton resulted in changes in the cells’ topology, height, and stiffness defined by Young’s modulus. Simultaneously, only for some A375 clones with a lowered Tβ4 level, we observed a decreased ability to initiate colony formation in soft agar, tumor formation in vivo, and alterations in Nanog’s expression level transcription factor regulating stemness. Thus, we show for the first time that in A375 cells, biomechanical properties are not directly coupled to stemness features, and this cell line is phenotypically heterogeneous.

scholarly journals lncRNA TUG1-Mediated Mir-142-3p Downregulation Contributes to Metastasis and the Epithelial-to-Mesenchymal Transition of Hepatocellular Carcinoma by Targeting ZEB1

2018 ◽  
Vol 48 (5) ◽  
pp. 1928-1941 ◽  
Author(s):  
Chuan He ◽  
Zhigang Liu ◽  
Li Jin ◽  
Fang Zhang ◽  
Xinhao Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Background/Aims: MicroRNA-142-3p (miR-142-3p) is dysregulated in many malignancies and may function as a tumor suppressor or oncogene in tumorigenesis and tumor development. However, few studies have investigated the clinical significance and biological function of miR-142-3p in hepatocellular carcinoma (HCC). Methods: The expression levels of taurine upregulated gene 1 (TUG1), miR-142-3p, and zinc finger E-box-binding homeobox 1 (ZEB1) were evaluated in HCC tissues and cell lines by quantitative real-time PCR. MTT and colony formation assays were used to detect cell proliferation ability, transwell assays were used to assess cell migration and invasion, and luciferase reporter assays were used to examine the interaction between the long noncoding RNA TUG1 and miR-142-3p. Tumor formation was evaluated through in vivo experiments. Results: miR-142-3p was significantly downregulated in HCC tissues, but TUG1 was upregulated in HCC tissues. Knockdown of TUG1 and upregulation of miR-142-3p inhibited cell proliferation, cell migration, cell invasion, and the epithelial-mesenchymal transition (EMT). miR-142-3p was found to be a prognostic factor of HCC, and the mechanism by which TUG1 upregulated ZEB1 was via direct binding to miR-142-3p. In vivo assays showed that TUG1 knockdown suppressed cell proliferation and the EMT in nude mice. Conclusion: The results of this study suggest that the TUG1/miR-142-3p/ ZEB1 axis contributes to the formation of malignant behaviors in HCC.

scholarly journals Suppression of MicroRNA 200 Family Expression by Oncogenic KRAS Activation Promotes Cell Survival and Epithelial-Mesenchymal Transition in KRAS-Driven Cancer

2016 ◽  
Vol 36 (21) ◽  
pp. 2742-2754 ◽  
Author(s):  
Xiaomin Zhong ◽  
Lan Zheng ◽  
Jianfeng Shen ◽  
Dongmei Zhang ◽  
Minmin Xiong ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Protein Translation ◽  
Cellular Transformation ◽  
Tumor Formation ◽  
Regulate Gene Expression ◽  
Mesenchymal Transition ◽  
Pancreatic Cancers ◽  
Mcf10a Cells

Oncogenic KRAS contributes to malignant transformation, antiapoptosis, and metastasis in multiple human cancers, such as lung, colon, and pancreatic cancers and melanoma. MicroRNAs (miRNAs) are endogenous 18- to 25-nucleotide noncoding small RNAs that regulate gene expression in a sequence-specific manner via the degradation of target mRNAs or inhibition of protein translation. In the present study, using array-based miRNA profiling in IMR90 and MCF10A cells expressing oncogenic KRAS, we identified that the expression of the microRNA 200 (mir-200) family was suppressed by KRAS activation and that this suppression was mediated by the transcription factors JUN and SP1 in addition to ZEB1. Restoration of mir-200 expression compromised KRAS-induced cellular transformationin vitroand tumor formationin vivo. In addition, we found that enforced expression of mir-200 abrogated KRAS-induced resistance to apoptosis by directly targeting the antiapoptotic geneBCL2. Finally, mir-200 was able to antagonize the epithelial-mesenchymal transition (EMT) driven by mutant KRAS. Collectively, our results suggest that repression of endogenous mir-200 expression is one of the important cellular responses to KRAS activation during tumor initiation and progression.

scholarly journals Phenotypic selection as the biological mode of epigenetic conversion and reversion in cell transformation

2018 ◽  
Vol 115 (4) ◽  
pp. E725-E732 ◽  
Author(s):  
Harry Rubin ◽  
Andrew L. Rubin
Keyword(s):  
Developmental Process ◽  
Epithelial Mesenchymal Transition ◽  
Phenotypic Selection ◽  
High Serum ◽  
Tumor Formation ◽  
X Rays ◽  
Focus Formation ◽  
Mesenchymal Transition

Exposure of certain cell lines to methylcholanthrene, X-rays, or physiological growth constraint leads to preneoplastic transformation in all or most of the treated cells. After attaining confluence, a fraction in those cells progress to full transformation, as evidenced by their ability to form discrete foci distinguishable from the surrounding cells by virtue of their higher density. Transformation induced by suspension in agar, an even stronger growth-selective condition than confluence, is reminiscent of all but the final differentiated stage of a normal developmental process, epithelial–mesenchymal transition. Changes associated with transformation are not restricted to focus-forming cells, as the permissiveness for focus formation provided by confluent cells surrounding transformed foci is greater than that of nonselected cells. The neoplastic process can also be reversed in culture. Transformed cells passaged at low density in high serum revert to normal morphology and growth behavior in vitro and lose the capacity for tumor formation in vivo. We propose that transformation and its reversal are driven by a process of phenotypic selection that involves entire heterogeneous populations of cells responding to microenvironmental changes. Because of the involvement of whole cell populations, we view this process as fundamentally adaptive and epigenetic in nature.

scholarly journals Elevated TRIP13 drives the AKT/mTOR pathway to induce the progression of hepatocellular carcinoma via interacting with ACTN4

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Meng-Xuan Zhu ◽  
Chuan-Yuan Wei ◽  
Peng-Fei Zhang ◽  
Dong-Mei Gao ◽  
Jie Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Thyroid Hormone Receptor ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Formation ◽  
Mtor Pathway ◽  
Clinicopathological Parameters ◽  
Mesenchymal Transition ◽  
Aaa Atpase

Abstract Background ATPase associated with a variety of cellular activities (AAA ATPase) family members are closely linked to tumor formation and progression. However, their roles in hepatocellular carcinoma (HCC) largely remain unclear. Methods Bioinformatic analyses of public databases were used to excavate the potential AAA ATPases that may contribute to HCC, and thyroid hormone receptor interactor 13 (TRIP13) was selected to following researches because of its most prominently differential expression. Western blot, qRT-PCR and immunohistochemistry were used to detect the expression of TRIP13 in HCC tissues, and then the relationship between TRIP13 expression and clinicopathological parameters were evaluated. Finally, its functions and potential mechanisms were investigated through a series gain- and loss-of-function strategies both in vitro and in vivo. Results TRIP13 was significantly overexpressed in HCC tissues and high level of TRIP13 was closely correlated with a worse clinical outcome. Functionally, elevated TRIP13 facilitated cell proliferation, migration, invasion, and promoted cellular epithelial–mesenchymal transition (EMT) in vitro, while promote tumor growth and lung metastasis in vivo. Mechanistically, TRIP13 interacted with ACTN4 and positively regulated its expression, thus activating the AKT/mTOR pathway to drive tumor progression. Moreover, miR-192-5p served as an upstream regulator of TRIP13 by directly binding to TRIP13 mRNA 3′ UTR, which may partially explain the high expression of TRIP13 in HCC. Conclusion Our findings identified TRIP13 as a promising candidate oncogene in HCC, and TRIP13 induced cell migration, invasion and metastasis of HCC through the AKT/mTOR signaling via interacting with ACTN4.

scholarly journals Effect of Huaier on Melanoma Invasion, Metastasis, and Angiogenesis

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Dongqiang Su ◽  
Bingbing Jiang ◽  
Yun Yang ◽  
Yu Miao ◽  
Qian Fu ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Hypoxia Inducible Factor ◽  
Treatment Strategies ◽  
Scientific Basis ◽  
Comprehensive Treatment ◽  
Melanoma Metastasis ◽  
Mesenchymal Transition ◽  
A375 Cells

Malignant melanoma (MM) is a highly metastatic and malignant cancer. Developing potential drugs with good efficacy and low toxicity for MM treatment is needed. Huaier, extracted from the mushroom Trametes robiniophila Murr, has been widely used in clinical anticancer treatments in China. A previous work done by our group confirmed that Huaier could inhibit cell proliferation and induce apoptosis in human melanoma cells. The current study is aimed at investigating the effects of Huaier on melanoma metastasis and angiogenesis in vitro and in vivo and to explore its possible mechanism of action. Our results showed that Huaier not only significantly inhibited the metastasis of A375 cells at the concentration ranging from 4 to 16 mg/ml (P<0.05), which were determined by the wound healing assay and transwell assay in vitro, but also suppressed the MM tumor growth and metastatic cells to the liver in A375-bearing mice after oral administration at the dose of 5 mg/kg (P<0.05). In addition, Huaier treatment downregulated the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), astrocyte-elevated gene-1 (AEG-1), and N-cadherin, while it upregulated E-cadherin expression in both the A375 cells and tumor tissues, which was detected using western blotting and RT-PCR (P<0.05). Taken together, our data suggests that the antitumor and antimetastatic activities of Huaier are caused by the downregulation of the HIF-1α/VEGF and AEG-1 signaling pathways and by the inhibition of epithelial-mesenchymal transition (EMT). This study provides a new insight into the mechanism of Huaier on antimetastatic therapy and a new scientific basis for comprehensive treatment strategies for MM.

scholarly journals miR-186 Suppresses the Progression of Cholangiocarcinoma Cells Through Inhibition of Twist1

2019 ◽  
Vol 27 (9) ◽  
pp. 1061-1068 ◽  
Author(s):  
Ming Zhang ◽  
Baochang Shi ◽  
Kai Zhang
Keyword(s):  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Formation ◽  
In Vitro Assays ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cycle Arrest

Deregulation of miR-186 and Twist1 has been identified to be involved in the progression of multiple cancers. However, the detailed molecular mechanisms underlying miR-186-involved cholangiocarcinoma (CCA) are still unknown. In this study, we found that miR-186 was downregulated in CCA tissues and cell lines, and negatively correlated with the expression of Twist1 protein. In vitro assays demonstrated that miR-186 mimics repressed cell proliferation, in vivo tumor formation, and caused cell cycle arrest. miR-186 mimics also inhibited the migration and invasion of CCLP1 and SG-231 cells. Mechanistically, the 3′-untranslated region (3′-UTR) of Twist1 mRNA is a direct target of miR-186. Further, miR-186 inhibited the expressions of Twist1, N-cadherin, vimentin, and matrix metallopeptidase 9 (MMP9) proteins, whereas it increased the expression of E-cadherin in CCLP1 and SG-231 cells. Silencing of Twist1 expression enhanced the inhibitory effects of miR-186 on the proliferation, migration, and invasion of CCLP1 and SG-231 cells. In conclusion, miR-186 inhibited cell proliferation, migration, invasion, and epithelial‐mesenchymal transition (EMT) through targeting Twist1 in human CCA. Thus, miR-186/Twist1 axis may benefit the development of therapies for CCA.

scholarly journals Roles of regulator of chromosome condensation 2 in cancer: Beyond its regulatory function in cell cycle

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Ali Calderon-Aparicio ◽  
Ann Bode
Keyword(s):  
Cell Cycle ◽  
Cancer Progression ◽  
Animal Studies ◽  
Epithelial Mesenchymal Transition ◽  
Cell Movement ◽  
Chromosome Condensation ◽  
Regulatory Function ◽  
Mesenchymal Transition

Regulator of chromosome condensation 2 (RCC2) is an essential protein in order for mitosis to proceed properly. It localizes in the centrosome of chromosomes where is involved in chromosome segregation and cytokinesis. Furthermore, RCC2 associates with integrin networks at the plasma membrane where participates in the control of cell movement. Because of its known role in cell cycle, RCC2 has been linked with cancer progression. Several reports show that RCC2 induces cancer hallmarks, but the mechanisms explaining how RCC2 exerts these roles are widely unknown. Here, we aim to summarize the main findings explaining the roles and mechanisms of RCC2 in cancer promotion. RCC2 is overexpressed in different cancers, including glioblastoma, lung, ovarian, and esophageal which is related to proliferation, migration, invasion promotion in vitro and tumor progression and metastasis in vivo. Besides, RCC2 overexpression induces epithelial-mesenchymal transition and causes poorer prognosis in cancer patients. RCC2 overexpression has also been linked with resistance development to chemotherapy and radiotherapy by inhibiting apoptosis and activating cancer-promoting transcription factors. Unfortunately, not RCC2 inhibitors are currently available for further pre-clinical and clinical assays. Therefore, these findings emphasize the potential use of RCC2 as a targetable biomarker in cancer and highlight the importance for designing RCC2 chemical inhibitors to evaluate its efficacy in animal studies and clinical trials.

Exposure to desflurane anesthesia confers colorectal cancer cells metastatic capacity through deregulation of miR-34a/LOXL3 

2020 ◽  
Author(s):  
Junyi Ren ◽  
Xiaopeng Wang ◽  
Gang Wei ◽  
Yajing Meng
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Protective Role ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Elevated Expression ◽  
Public Datasets

Abstract Background: Due to high potency and low toxicity, desflurane has been wildly used during surgery. Recent evidence that the use of desflurane was associated with colorectal cancer (CRC) tumor metastasis and poor prognosis raising concerns about the safety of desflurane. However, the mechanism was uncovered.Methods: CRC cells were exposed to desflurane, the changes in morphology and epithelial-mesenchymal transition (EMT)-related genes were evaluated. Transwell assay was used to study the migration and invasion effect. Xenograft was performed to study the tumor formation ability of desflurane-treated cells in vivo. Dual luciferase reporter assay was conducted to verify the target of miR-34a. Knockdown or overexpression of LOXL3 was used to investigate the mechanism of desflurane-induced EMT. The association of LOXL3 with CRC molecular subtypes and clinical relevance was studied by analysis of public datasets. Results: Exposure to desflurane induced EMT, migration, and invasion in CRC cells. Mice injected with desflurane-treated cells formed more tumors in the lungs. Downregulation of miR-34a and upregulation of LOXL3 were required for desflurane-induced EMT in CRC cells. LOXL3 was a direct target of miR-34a. Overexpression of LOXL3 rescued miR-34a-repressed EMT after exposure to desflurane. Elevated expression of LOXL3 was enriched in CMS4 and CRIS-B subtypes. Patients with high expression of LOXL3 showed more lymph node metastasis, as well as poor survival.Conclusion: Desflurane induced EMT and metastasis in CRC through deregulation of miR-34a/LOXL3 axis. Clinical miR-34a mimic or inhibitor targeting LOXL3 might have a potential protective role when CRC patients anesthetized by desflurane.

scholarly journals LincHOXA10 Facilitates Colorectal Cancer Development By Regulating HOXA10-Mediated Epithelial-Mesenchymal Transtion

2020 ◽  
Author(s):  
Huifang Zhu ◽  
Yongzhen Li ◽  
Yinghui Zhang ◽  
Zheying Zhang ◽  
Yongxia Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Tumor Formation ◽  
Migration And Invasion ◽  
Tissue Samples ◽  
Mesenchymal Transition

Abstract Background: Long non-coding RNAs (lncRNAs) have been reported to play an important role in tumorigenesis and metastasis of human colorectal cancer (CRC). However, the specific role of LincHOXA10 in CRC remains unknown.Methods: The expression of LincHOXA10 and HOXA10 in CRC cells and tissue samples was measured by quantitative reverse transcription PCR (qRT-PCR). The protein expression of HOXA10, E-cadherin, N-cadherin, Vinmentin, p-smad2 and p-smad3 was assessed by Western blotting or immunofluorescence staining. Cell proliferation, migration, and invasion were assessed by the MTT and transwell assays. Tumor growth in vivo was carried out by subcutaneous tumor formation in nude mice.Results: In the present study, we found that LincHOXA10 expression was significantly higher in human CRC tissues than the paired normal tissues. In fact, LincHOXA10 level correlated with the CRC tumor sizes and lymphatic metastasis. In cultured CRC cells, knockdown of LincHOXA10 inhibited cell proliferation, migration and invasion. LincHOXA10 deficiency also attenuated CRC tumor growth in vivo. Mechanistically, LincHOXA10 interacted with HOXA10 and regulated its expression. HOXA10 levels were interrelated to the LincHOXA10 level in CRC cells. Functionally, HOXA10 was essential for TGF-β1/SMADs-induced epithelial -mesenchymal transition of CRC cells, and HOXA10 played a critical role in mediating the function of LincHOXA10. Importantly, HOXA10 expression was significantly up-regulated in human CRC tissues.Conclusions: LincHOXA10 facilitates CRC development and metastasis via regulating HOXA10-mediated epithelial-mesenchymal transition of CRC cells.

scholarly journals Downregulation of circ_0037655 impedes glioma formation and metastasis via the regulation of miR-1229-3p/ITGB8 axis

2021 ◽  
Vol 16 (1) ◽  
pp. 442-454
Author(s):  
Wenhui Zou ◽  
Yalei Cao ◽  
Kai Cheng ◽  
Changyu Li ◽  
Fu Zhu ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Mesenchymal Transition ◽  
Circular Rna ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Scratch Assay ◽  
Mesenchymal Transition ◽  
Glioma Progression

Abstract Background Glioma is the most frequent, highly aggressive primary intracranial malignant tumor. Circular RNA (circRNA) circ_0037655 has been reported to be a vital regulator in glioma. The different functional mechanism behind circ_0037655 was investigated in the current study. Methods The expression of circ_0037655, microRNA-1229-3p (miR-1229-3p) and integrin beta-8 (ITGB8) was detected via the quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Cellular research was performed via colony formation assay for cell proliferation, flow cytometry for cell cycle and cell apoptosis, scratch assay for cell migration, as well as transwell assay for cell migration and invasion. Western blot was used for detection of ITGB8 protein and epithelial–mesenchymal transition (EMT) process. Dual-luciferase reporter assay was implemented for the binding analysis of potential targets. In vivo assay was administered via xenograft in mice. Results Upregulation of circ_0037655 was affirmed in glioma samples and cells. Tumor formation and metastasis of glioma were inhibited after circ_0037655 was downregulated. miR-1229-3p acted as a target of circ_0037655, and its upregulation was responsible for the function of si-circ_0037655 in glioma cells. miR-1229-3p functioned as a tumor inhibitor in glioma progression by targeting ITGB8. circ_0037655 modulated the ITGB8 expression by targeting miR-1229-3p. In vivo knockdown of circ_0037655 also suppressed glioma tumorigenesis by acting on the miR-1229-3p/ITGB8 axis. Conclusion This study showed that downregulation of the expression of circ_0037655 could inhibit glioma progression by acting on the miR-1229-3p/ITGB8 axis. The specific circ_0037655/miR-1229-3p/ITGB8 axis was disclosed in glioma research.

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