scholarly journals Knockdown of lncRNA NUTM2A‑AS1 inhibits lung adenocarcinoma cell viability by regulating the miR‑590‑5p/METTL3 axis

2021 ◽  
Vol 22 (5) ◽  
Author(s):  
Jie Wang ◽  
Jingyun Zha ◽  
Xiaolin Wang
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Viability ◽  
Adenocarcinoma Cell

PIM2 promotes lung adenocarcinoma cell migration by regulating XIAP/NF-κB pathway

2021 ◽  
Keyword(s):  
Cell Migration ◽  
Western Blot ◽  
Lung Adenocarcinoma ◽  
Cell Viability ◽  
Adenocarcinoma Cell ◽  
Invasion And Migration ◽  
Over Expression ◽  
Apoptosis Protein ◽  
Iκbα Phosphorylation ◽  
And Migration

Background and objective: Proviral insertion site in Moloney murine leukemia virus (PIM)2 functions as a serine/threonine kinase to participate in regulating cell proliferation and cell cycle. PIM2 has been shown to be elevated in the lung cancer cell lines. This study was performed to investigate the role of PIM2 in lung adenocarcinoma cell growth. Mateial and methods: Expression level of PIM2 in lung adenocarcinoma tissues and cells was detected by qRT-PCR (quantitative Reverse Transcription PCR) and western blot. The over-expression and knockdown of PIM2 were separately established by employing pcDNA and siRNA to explore the effects on the cell viability, apoptosis, invasion and migration. The downstream pathways were evaluated by western blot assay. Results: Lung adenocarcinoma tissues and cells showed an elevation of both PIM2 mRNA and protein expression. Knocking down PIM2 decreased the cell viability and promoted the apoptosis, which can be reversed by pcDNA-mediated over-expression of PIM2. PIM2 silencing suppressed the promotional effect of over-expression of PIM2 on cell invasion and migration through increasing IκBα expression and decreasing the X-linked inhibitor of apoptosis protein (XIAP), p65 and IκBα phosphorylation. While, over-expression of PIM2 showed opposite effect on IκBα and XIAP expression or p65 and IκBα phosphorylation. Conclusion: PIM2 can not only suppress lung adenocarcinoma cell apoptosis but also promote cell migration and invasion depending on XIAP/NF-κB signaling pathway.

scholarly journals Upregulation of centromere protein K is crucial for lung adenocarcinoma cell viability and invasion

2021 ◽  
Vol 30 (7) ◽  
pp. 0-0
Author(s):  
Yongbo Wang ◽  
Yue Wang ◽  
Chunna Ren ◽  
Haicun Wang ◽  
Yang Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Viability ◽  
Adenocarcinoma Cell ◽  
Centromere Protein

scholarly journals UBR-Box containing protein, UBR5, is over-expressed in human lung adenocarcinoma and is a potential therapeutic target

2020 ◽  
Author(s):  
Kumar Saurabh ◽  
Parag P. Shah ◽  
Mark A. Doll ◽  
Leah J. Siskind ◽  
Levi J. Beverly
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cell Viability ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Human Lung ◽  
Human Patient ◽  
Adenocarcinoma Cell ◽  
Ubiquitination Pathway

AbstractBackgroundN-end rule ubiquitination pathway is known to be disrupted in many diseases, including cancer. UBR5, an E3 ubiquitin ligase, is mutated and/or overexpressed in human lung cancer cells suggesting its pathological role in cancer.MethodsWe determined expression of UBR5 protein in multiple lung cancer cell lines and human patient samples. Using immunoprecipitation followed by mass spectrometry we determined the UBR5 interacting proteins. The impact of loss of UBR5 for lung adenocarcinoma cell lines was analyzed using cell viability, clonogenic assays and in vivo xenograft models in nude mice. Additional Western blot analysis was performed to assess the loss of UBR5 on downstream signaling. Statistical analysis was done by one-way ANOVA for in vitro studies and Wilcoxon paired t-test for tumor volumes in vivo.ResultsWe show variability of UBR5 expression levels in lung adenocarcinoma cell lines and in primary human patient samples. To gain better insight into the role that UBR5 may play in lung cancer progression we performed unbiased interactome analyses for UBR5. Data indicate that UBR5 has a wide range of interacting protein partners that are known to be involved in critical cellular processes such as DNA damage, proliferation and cell cycle regulation. We have demonstrated that shRNA-mediated loss of UBR5 decreases cell viability and clonogenic potential of lung adenocarcinoma cell lines. In addition, we found decreased levels of activated AKT signaling after the loss of UBR5 in lung adenocarcinoma cell lines using multiple means of UBR5 knockdown/knockout. Furthermore, we demonstrated that loss of UBR5 in lung adenocarcinoma cells results in significant reduction of tumor volume in nude mice.ConclusionsThese findings demonstrate that deregulation of the N-end rule ubiquitination pathway plays a crucial role in the etiology of some human cancers, and blocking this pathway via UBR5-specific inhibitors, may represent a unique therapeutic target for human cancers.

scholarly journals UBR-Box containing protein, UBR5, is over-expressed in human lung adenocarcinoma and is a potential therapeutic target

2020 ◽  
Author(s):  
Kumar Saurabh ◽  
Parag P Shah ◽  
Mark Doll ◽  
Leah J Siskind ◽  
Levi J. Beverly
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cell Viability ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Human Lung ◽  
Human Patient ◽  
Adenocarcinoma Cell ◽  
Ubiquitination Pathway

Abstract Background: N-end rule ubiquitination pathway is known to be disrupted in many diseases, including cancer. UBR5, an E3 ubiquitin ligase, is mutated and/or overexpressed in human lung cancer cells suggesting its pathological role in cancer. Methods: We determined expression of UBR5 protein in multiple lung cancer cell lines and human patient samples. Using immunoprecipitation followed by mass spectrometry we determined the UBR5 interacting proteins. The impact of loss of UBR5 for lung adenocarcinoma cell lines was analyzed using cell viability, clonogenic assays and in vivo xenograft models in nude mice. Additional Western blot analysis was performed to assess the loss of UBR5 on downstream signaling. Statistical analysis was done by one-way ANOVA for in vitro studies and Wilcoxon paired t-test for tumor volumes in vivo. Results: We show variability of UBR5 expression levels in lung adenocarcinoma cell lines and in primary human patient samples. To gain better insight into the role that UBR5 may play in lung cancer progression we performed unbiased interactome analyses for UBR5. Data indicate that UBR5 has a wide range of interacting protein partners that are known to be involved in critical cellular processes such as DNA damage, proliferation and cell cycle regulation. We have demonstrated that shRNA-mediated loss of UBR5 decreases cell viability and clonogenic potential of lung adenocarcinoma cell lines. In addition, we found decreased levels of activated AKT signaling after the loss of UBR5 in lung adenocarcinoma cell lines using multiple means of UBR5 knockdown/knockout. Furthermore, we demonstrated that loss of UBR5 in lung adenocarcinoma cells results in significant reduction of tumor volume in nude mice. Conclusions: These findings demonstrate that deregulation of the N-end rule ubiquitination pathway plays a crucial role in the etiology of some human cancers, and blocking this pathway via UBR5-specific inhibitors, may represent a unique therapeutic target for human cancers.

scholarly journals UBR-Box containing protein, UBR5, is over-expressed in human lung adenocarcinoma and is a potential therapeutic target

2020 ◽  
Author(s):  
Kumar Saurabh ◽  
Parag P Shah ◽  
Mark Doll ◽  
Leah J Siskind ◽  
Levi J. Beverly
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cell Viability ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Human Lung ◽  
Human Patient ◽  
Adenocarcinoma Cell ◽  
Ubiquitination Pathway

Abstract Background: N-end rule ubiquitination pathway is known to be disrupted in many diseases, including cancer. UBR5, an E3 ubiquitin ligase, is mutated and/or overexpressed in human lung cancer cells suggesting its pathological role in cancer. Methods: We determined expression of UBR5 protein in multiple lung cancer cell lines and human patient samples. Using immunoprecipitation followed by mass spectrometry we determined the UBR5 interacting proteins. The impact of loss of UBR5 for lung adenocarcinoma cell lines was analyzed using cell viability, clonogenic assays and in vivo xenograft models in nude mice. Additional Western blot analysis was performed to assess the loss of UBR5 on downstream signaling. Statistical analysis was done by one-way ANOVA for in vitro studies and Wilcoxon paired t-test for tumor volumes in vivo. Results: We show variability of UBR5 expression levels in lung adenocarcinoma cell lines and in primary human patient samples. To gain better insight into the role that UBR5 may play in lung cancer progression we performed unbiased interactome analyses for UBR5. Data indicate that UBR5 has a wide range of interacting protein partners that are known to be involved in critical cellular processes such as DNA damage, proliferation and cell cycle regulation. We have demonstrated that shRNA-mediated loss of UBR5 decreases cell viability and clonogenic potential of lung adenocarcinoma cell lines. In addition, we found decreased levels of activated AKT signaling after the loss of UBR5 in lung adenocarcinoma cell lines using multiple means of UBR5 knockdown/knockout. Furthermore, we demonstrated that loss of UBR5 in lung adenocarcinoma cells results in significant reduction of tumor volume in nude mice. Conclusions: These findings demonstrate that deregulation of the N-end rule ubiquitination pathway plays a crucial role in the etiology of some human cancers, and blocking this pathway via UBR5-specific inhibitors, may represent a unique therapeutic target for human cancers.

Isoorientin Decreases Cell Migration via Decreasing Functional Activity and Molecular Expression of Proton-Linked Monocarboxylate Transporters in Human Lung Cancer Cells

2020 ◽  
Vol 48 (01) ◽  
pp. 201-222
Author(s):  
Hsu-Kai Huang ◽  
Shin-Yi Lee ◽  
Shu-Fen Huang ◽  
Yu-San Lin ◽  
Shih-Chi Chao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Lung Adenocarcinoma ◽  
Cell Viability ◽  
Cancer Cells ◽  
Functional Activity ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Human Lung Cancer Cells

Aggressive tumor cells mainly rely on glycolysis, and further release vast amounts of lactate and protons by monocarboxylate transporter (MCT), which causes a higher intracellular pH (pHi) and acidic extracellular pH. Isoorientin, a principle flavonoid compound extracted from several plant species, shows various pharmacological activities. However, effects of isoorientin on anticancer and MCT await to explore in human lung cancer cells. Human lung cancer tissues were obtained from cancer patients undergoing surgery, while the human lung adenocarcinoma cells (A549) were bought commercially. Change of pHi was detected by microspectrofluorometry method with a pH-sensitive fluorescent dye, BCECF. MTT and wound-healing assay were used to detect the cell viability and migration, respectively. Western blot techniques and immunocytochemistry staining were used to detect the protein expression. Our results indicated that the expression of MCTs1/4 and CD147 were upregulated significantly in human lung tissues. In experiments of A549 cells, under HEPES-buffer, the resting pHi was 7.47, and isoorientin (1–300[Formula: see text][Formula: see text]M) inhibited functional activity of MCT concentration-dependently (up to [Formula: see text]%). Pretreatment with isoorientin (3–100[Formula: see text][Formula: see text]M) for 24[Formula: see text]h, MCT activity and cell migration were significantly inhibited ([Formula: see text]% and [Formula: see text]%, respectively), while the cell viability was not affected. Moreover, the expression of MCTs1/4, CD147, and matrix metalloproteinase (MMP) 2/9 were significantly down regulated. In summary, MCTs1/4 and CD147 are significantly upregulated in human lung adenocarcinoma tissues, and isoorientin inhibits cells-migration by inhibiting activity/expression of MCTs1/4 and MMPs2/9 in human lung cancer cells. These novel findings suggest that isoorientin could be a promising pharmacological agent for lung cancer.

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