Phenethyl Isothiocyanate (PEITC) and Benzyl Isothiocyanate (BITC) Inhibit Human Melanoma A375.S2 Cell Migration and Invasion by Affecting MAPK Signaling Pathway In Vitro

Abstract Background Accumulation evidence indicates the vital role of long non-coding RNAs (lncRNAs) in tumorigenesis and the progression of malignant tumors, including pancreatic cancer (PC). However, the role and the molecular mechanism of long non-coding RNA 00976 is unclear in pancreatic cancer. Methods In situ hybridization (ISH) and qRT-PCR was performed to investigate the association between linc00976 expression and the clinicopathological characteristics and prognosis of patients with PC. Subsequently, linc00976 over-expression vector and shRNAs were transfected into PC cells to up-regulate or down-regulate linc00976 expression. Loss- and gain-of function assays were performed to investigate the role of linc00976 in proliferation and metastasis in vitro and vivo. ITRAQ, bioinformatic analysis and rescue assay were used to illustrate the ceRNA mechanism network of linc00976/miR-137/OTUD7B and its downstream EGFR/MAPK signaling pathway. Results linc00976 expression was overexpressed in PC tissues and cell lines and was positively associated with poorer survival in patients with PC. Function studies revealed that linc00976 knockdown significantly suppressed cell proliferation, migration and invasion in vivo and in vitro, whereas its overexpression reversed these effects. Based on Itraq results and online database prediction, Ovarian tumor proteases OTUD7B was found as a downstream gene of linc00976, which deubiquitinated EGFR mediates MAPK signaling activation. Furthermore, Bioinformatics analysis and luciferase assays and rescue experiments revealed that linc00976/miR137/OTUD7B established the ceRNA network modulating PC cell proliferation and tumor growth. Conclusion The present study demonstrates that linc00976 enhances the proliferation and invasion ability of PC cells by upregulating OTUD7B expression, which was a target of miR-137. Ultimately, OTUD7B mediates EGFR and MAPK signaling pathway, suggesting that linc00976/miR-137/OTUD7B/EGFR axis may act as a potential biomarker and therapeutic target for PC.

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tRNA-Derived Fragment tRF-Glu-TTC-027 Regulates the Progression of Gastric Carcinoma via MAPK Signaling Pathway

Frontiers in Oncology ◽

10.3389/fonc.2021.733763 ◽

2021 ◽

Vol 11 ◽

Author(s):

Weiguo Xu ◽

Bin Zhou ◽

Juan Wang ◽

Li Tang ◽

Qing Hu ◽

...

Keyword(s):

Gastric Carcinoma ◽

Signaling Pathway ◽

Cell Lines ◽

Mapk Pathway ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Migration And Invasion ◽

Underlying Mechanisms

Transfer RNA-derived RNA fragments (tRFs) belong to non-coding RNAs (ncRNAs) discovered in most carcinomas. Although some articles have demonstrated the characteristics of tRFs in gastric carcinoma (GC), the underlying mechanisms still need to be elucidated. Meanwhile, it was reported that the MAPK pathway was momentous in GC progression. Thus we focused on investigating whether tRF-Glu-TTC-027 could act as a key role in the progression of GC with the regulation of the MAPK pathway. We collected the data of the tRNA-derived fragments expression profile from six paired clinical GC tissues and corresponding adjacent normal samples in this study. Then we screened tRF-Glu-TTC-027 for analysis by using RT-PCR. We transfected GC cell lines with tRF-Glu-TTC-027 mimics or mimics control. Then the proliferation, migration, and invasion assays were performed to assess the influence of tRF-Glu-TTC-027 on GC cell lines. Fluorescence in situ hybridization assay was conducted to confirm the cell distribution of tRF-Glu-TTC-027. We confirmed the mechanism that tRF-Glu-TTC-027 influenced the MAPK signaling pathway and observed a strong downregulation of tRF-Glu-TTC-027 in clinical GC samples. Overexpression of tRF-Glu-TTC-027 suppressed the malignant activities of GC in vitro and in vivo. MAPK signaling pathway was confirmed to be a target pathway of tRF-Glu-TTC-027 in GC by western blot. This is the first study to show that tRF-Glu-TTC-027 was a new tumor-suppressor and could be a potential object for molecular targeted therapy in GC.

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Natural compound rhein suppresses colorectal cancer cells growth through mTOR/p70S6 kinase pathway in vitro and in vivo

10.21203/rs.3.rs-41306/v1 ◽

2020 ◽

Author(s):

Haibo Zhang ◽

Song Park ◽

Hai Huang ◽

Jun koo Yi ◽

Sijun Park ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Cycle ◽

Cell Migration ◽

Cell Growth ◽

Signaling Pathway ◽

Migration And Invasion ◽

P70s6 Kinase ◽

Cell Migration And Invasion

Abstract Background: Rhein is a natural agent isolated from the traditional Chinese medicine rhubarb, which has been used as a medicine in China since ancient times. Although rhein was found to have significant anticancer effects in different cancer models, the effect and the underlying mechanisms of action of rhein in colorectal cancer (CRC) remain unclear. The mTOR/p70S6 kinase (p70S6K) pathway has been demonstrated as an attractive target for developing novel cancer therapeutics.Methods: The human CRC cell lines HCT116, HCT15, and DLD1 and xenograft mice were used in this study to investigate the effects of rhein. Assessments of cellular morphology, cell proliferation, and anchorage-independent colony formation were performed to examine the effects of rhein on cell growth. Wound healing assay and transwell migration and invasion assay were conducted to detect cell migration and invasion. Cell cycle and apoptosis were investigated by flow cytometry and verified by immunoblotting. Tissue microarray was used to detect mTOR expression in patients with CRC. Gene overexpression and knockdown were implemented to analyze the function of mTOR in CRC. The in vivo effect of rhein was assessed in a xenograft mouse model.Results: Rhein significantly inhibited CRC cell growth by inducing S phase cell cycle arrest and apoptosis. It also inhibited CRC cell migration and invasion ability through EMT process. mTOR was highly expression in CRC cancer tissues and cells exhibited high mTOR expression. Overexpression of mTOR promoted cell growth, migration, and invasion ability, whereas mTOR knockdown diminished these phenomena of CRC cells in vitro. Moreover, rhein directly targeted mTOR and suppressed the mTOR/p70S6K signaling pathway in CRC cells. Intraperitoneal administration of rhein inhibited CRC cell HCT116 xenograft tumor growth through the mTOR/p70S6K pathway.Conclusions: Rhein exerted anticancer activity in vitro and in vivo through directly targeting mTOR and inhibiting mTOR/p70S6K signaling pathway. These data indicate that rhein is a potent anticancer agent that could be useful for the prevention or treatment of CRC.

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Fistein Suppresses Human Osteosarcoma U-2 OS Cell Migration and Invasion via Affecting FAK, uPA and NF-ĸB Signaling Pathway In Vitro

In Vivo ◽

10.21873/invivo.11542 ◽

2019 ◽

Vol 33 (3) ◽

pp. 801-810 ◽

Cited By ~ 8

Author(s):

JR-KAI CHEN ◽

SHU-FEN PENG ◽

KUANG CHI LAI ◽

HSIN-CHUNG LIU ◽

YI-PING HUANG ◽

...

Keyword(s):

Cell Migration ◽

Signaling Pathway ◽

Migration And Invasion ◽

Cell Migration And Invasion ◽

Human Osteosarcoma

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ARHGAP4 regulates the cell migration and invasion of pancreatic cancer by the HDAC2/β-catenin signaling pathway

Carcinogenesis ◽

10.1093/carcin/bgz067 ◽

2019 ◽

Vol 40 (11) ◽

pp. 1405-1414 ◽

Cited By ~ 1

Author(s):

Yehua Shen ◽

Litao Xu ◽

Zhouyu Ning ◽

Luming Liu ◽

Junhua Lin ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cell Migration ◽

Signaling Pathway ◽

Critical Role ◽

Wnt Signaling Pathway ◽

Migration And Invasion ◽

Cell Migration And Invasion ◽

Histone Deacetylase 2 ◽

Pancreatic Cancer Cells

Abstract β-catenin is a subunit of the cadherin protein complex and acts as an intracellular signal transducer in the Wnt signaling pathway that mediates multiple cellular processes, such as cell migration and invasion. HDAC2 (histone deacetylase 2), a deacetylase that maintains histone H3 in a deacetylated state in the promoter region of Wnt-targeted genes where β-catenin is bound, negatively regulating β-catenin activation. However, the regulation of HDAC2/β-catenin pathway remains unclear. Here, we report ARHGAP4 as a new regulator of the β-catenin pathway that regulates cell invasion and migration of pancreatic cancer as well as the downstream effector MMP2 and MMP9 expression in vitro. Mechanistically, ARHGAP4 interacts with and ubiquitinates HDAC2, which in turn inhibits β-catenin activation. Furthermore, treatment of CAY10683, an HDAC2 inhibitor, and XAV939, a Wnt/β-catenin pathway inhibitor, attenuated the effects of ARHGAP4 silencing on pancreatic cancer cells. Overall, our findings establish ARHGAP4 as a novel regulator of HDAC2/β-catenin pathway with a critical role in tumorigenesis.

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Berberine Inhibits Human Melanoma A375.S2 Cell Migration and Invasion via Affecting the FAK, uPA, and NF-κB Signaling Pathways and Inhibits PLX4032 Resistant A375.S2 Cell Migration In Vitro

Molecules ◽

10.3390/molecules23082019 ◽

2018 ◽

Vol 23 (8) ◽

pp. 2019 ◽

Cited By ~ 4

Author(s):

Jia-Fang Liu ◽

Kuang Lai ◽

Shu-Fen Peng ◽

Pornsuda Maraming ◽

Yi-Ping Huang ◽

...

Keyword(s):

Cell Migration ◽

Cancer Cells ◽

Gelatin Zymography ◽

Cell Number ◽

Human Melanoma ◽

Migration And Invasion ◽

Viable Cell Number ◽

S2 Cells ◽

Cell Migration And Invasion

Many studies have demonstrated that berberine inhibited the cell migration and invasion in human cancer cell lines. However, the exact molecular mechanism of berberine inhibiting the cell migration and invasion of human melanoma A375.S2 and A375.S2/PLX (PLX4032 induced resistant A375.S2) skin cancer cells remains unknown. In this study, we investigated the anti-metastasis mechanisms of berberine in human melanoma cancer A375.S2 cells and A375.S2/PLX resistant cells in vitro. Berberine at low concentrations (0, 1, 1.5 and 2 μM) induced cell morphological changes and reduced the viable cell number and inhibited the mobility, migration, and invasion of A375.S2 cells that were assayed by wound healing and transwell filter. The gelatin zymography assay showed that berberine slightly inhibited MMP-9 activity in A375.S2 cells. Results from western blotting indicated that berberine inhibited the expression of MMP-1, MMP-13, E-cadherin, N-cadherin, RhoA, ROCK1, SOS-1, GRB2, Ras, p-ERK1/2, p-c-Jun, p-FAK, p-AKT, NF-κB, and uPA after 24 h of treatment, but increased the PKC and PI3K in A375.S2 cells. PLX4032 is an inhibitor of the BRAFV600E mutation and used for the treatment of cancer cells harboring activated BRAF mutations. Berberine decrease cell number and inhibited the cell mobility in the resistant A375.S2 (A375.S2/PLX, PLX4032 generated resistant A375.S2 cells). Based on these observations, we suggest that the potential of berberine as an anti-metastatic agent in melanoma that deserves to be investigated in more detail, including in vivo studies in future.

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