Clinical significance of the phosphorylation of MAPK and protein expression of cyclin D1 in human osteosarcoma tissues

Abstract Background Emerging evidence confirms that lncRNAs (long non-coding RNAs) are potential biomarkers that play vital roles in tumors. ZNF582-AS1 is a novel lncRNA that serves as a potential prognostic marker of cancers. However, the specific clinical significance and molecular mechanism of ZNF582-AS1 in ccRCC (clear cell renal cell carcinoma) are unclear. Methods Expression level and clinical significance of ZNF582-AS1 were determined by TCGA-KIRC data and qRT-PCR results of 62 ccRCCs. DNA methylation status of ZNF582-AS1 promoter was examined by MSP, MassARRAY methylation and demethylation analysis. Gain-of-function experiments were conducted to investigate the biological roles of ZNF582-AS1 in the phenotype of ccRCC. The subcellular localization of ZNF582-AS1 was detected by RNA FISH. iTRAQ, RNA pull-down and RIP-qRT-PCR were used to identify the downstream targets of ZNF582-AS1. rRNA MeRIP-seq and MeRIP-qRT-PCR were utilized to examine the N(6)-methyladenosine modification status. Western blot and immunohistochemistry assays were used to determine the protein expression level. Results ZNF582-AS1 was downregulated in ccRCC, and decreased ZNF582-AS1 expression was significantly correlated with advanced tumor stage, higher pathological stage, distant metastasis and poor prognosis. Decreased ZNF582-AS1 expression was caused by DNA methylation at the CpG islands within its promoter. ZNF582-AS1 overexpression inhibited cell proliferative, migratory and invasive ability, and increased cell apoptotic rate in vitro and in vivo. Mechanistically, we found that ZNF582-AS1 overexpression suppressed the N(6)-methyladenosine modification of MT-RNR1 by reducing rRNA adenine N(6)-methyltransferase A8K0B9 protein level, resulting in the decrease of MT-RNR1 expression, followed by the inhibition of MT-CO2 protein expression. Furthermore, MT-RNR1 overexpression reversed the decreased MT-CO2 expression and phenotype inhibition of ccRCC induced by increased ZNF582-AS1 expression. Conclusions This study demonstrates for the first time that ZNF582-AS1 functions as a tumor suppressor gene in ccRCC and ZNF582-AS1 may serve as a potential biomarker and therapeutic target of ccRCC.

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mTOR function in skeletal muscle hypertrophy: increased ribosomal RNA via cell cycle regulators

AJP Cell Physiology ◽

10.1152/ajpcell.00165.2005 ◽

2005 ◽

Vol 289 (6) ◽

pp. C1457-C1465 ◽

Cited By ~ 104

Author(s):

Gustavo A. Nader ◽

Thomas J. McLoughlin ◽

Karyn A. Esser

Keyword(s):

Cell Cycle ◽

Protein Expression ◽

Cyclin D1 ◽

Ribosomal Rna ◽

Molecular Mechanisms ◽

D1 Protein ◽

Rna Content ◽

Cyclin D1 Protein ◽

Rb Phosphorylation ◽

Myotube Hypertrophy

The purpose of this study was to identify the potential downstream functions associated with mammalian target of rapamycin (mTOR) signaling during myotube hypertrophy. Terminally differentiated myotubes were serum stimulated for 3, 6, 12, 24, and 48 h. This treatment resulted in significant myotube hypertrophy (protein/DNA) and increased RNA content (RNA/DNA) with no changes in DNA content or indices of cell proliferation. During myotube hypertrophy, the increase in RNA content was accompanied by an increase in tumor suppressor protein retinoblastoma (Rb) phosphorylation and a corresponding increase in the availability of the ribosomal DNA transcription factor upstream binding factor (UBF). Serum stimulation also induced an increase in cyclin D1 protein expression in the differentiated myotubes with a concomitant increase in cyclin D1-dependent cyclin-dependent kinase (CDK)-4 activity toward Rb. The increases in myotube hypertrophy and RNA content were blocked by rapamycin treatment, which also prevented the increase in cyclin D1 protein expression, CDK-4 activity, Rb phosphorylation, and the increase in UBF availability. Our findings demonstrate that activation of mTOR is necessary for myotube hypertrophy and suggest that the role of mTOR is in part to modulate cyclin D1-dependent CDK-4 activity in the regulation of Rb and ribosomal RNA synthesis. On the basis of these results, we propose that common molecular mechanisms contribute to the regulation of myotube hypertrophy and growth during the G1 phase of the cell cycle.

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Elevated protein expression of cyclin D1 and Fra-1 but decreased expression of c-Myc in human colorectal adenocarcinomas overexpressing ?-catenin

International Journal of Cancer ◽

10.1002/ijc.10630 ◽

2002 ◽

Vol 101 (4) ◽

pp. 301-310 ◽

Cited By ~ 44

Author(s):

Hanlin L. Wang ◽

Julia Wang ◽

Shu-Yuan Xiao ◽

Rex Haydon ◽

Debra Stoiber ◽

...

Keyword(s):

Protein Expression ◽

Cyclin D1 ◽

Elevated Protein ◽

Colorectal Adenocarcinomas

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Clinical significance of gelsolin-like actin-capping protein expression in oral carcinogenesis: an immunohistochemical study of premalignant and malignant lesions of the oral cavity

BMC Cancer ◽

10.1186/1471-2407-8-39 ◽

2008 ◽

Vol 8 (1) ◽

Cited By ~ 27

Author(s):

Hitomi Nomura ◽

Katsuhiro Uzawa ◽

Takashi Ishigami ◽

Yukinao Kouzu ◽

Hirofumi Koike ◽

...

Keyword(s):

Oral Cavity ◽

Protein Expression ◽

Clinical Significance ◽

Immunohistochemical Study ◽

Capping Protein ◽

Oral Carcinogenesis ◽

Actin Capping Protein ◽

Malignant Lesions ◽

Actin Capping

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IMP3 Protein Overexpression Is Linked to Unfavorable Outcome in Laryngeal Squamous Cell Carcinoma

Cancers ◽

10.3390/cancers13174306 ◽

2021 ◽

Vol 13 (17) ◽

pp. 4306

Author(s):

Diana Maržić ◽

Blažen Marijić ◽

Tamara Braut ◽

Stefan Janik ◽

Manuela Avirović ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Protein Expression ◽

Cell Carcinoma ◽

Cyclin D1 ◽

Squamous Cell ◽

Expression Patterns ◽

Low Grade ◽

Benign Lesions ◽

Ki 67 ◽

Neck Node

Background: The aim of this study was to (i) determine IMP3 protein expression in benign and malignant laryngeal lesions, (ii) compare its expression to Ki-67, p53, cyclin D1, and (iii) finally, to examine the prognostic power of IMP3 in squamous cell carcinomas of the larynx (LSSC). Methods: IMP3 protein expression was evaluated in 145 patients, including 62 LSCC, 45 dysplasia (25 with low and 20 with high-grade dysplasia), and 38 benign lesions (vocal cord polyps and nodules). Results: IMP3 was significantly higher expressed in LSCC compared to dysplasia and benign lesions (p < 0.001; p < 0.001, respectively). Similarly, higher expression patterns were observed for Ki-67 and p53, whereas cyclin D1 was equally distributed in all three lesions. IMP3 (p = 0.04) and Ki-67 (p = 0.02) expressions were significantly linked to neck node positivity, and IMP3 overexpression to worse disease-specific survival (p = 0.027). Conclusion: Since IMP3 showed significantly higher expression in laryngeal carcinomas, but not in high- or low-grade dysplasia, it serves as a useful marker to differentiate between invasive and noninvasive lesions. Higher IMP3 expression represented a significantly worse prognosticator for clinical outcomes of patients with squamous cell carcinoma of the larynx.

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Clinical significance of Reg IV protein expression in human colorectal cancer

World Chinese Journal of Digestology ◽

10.11569/wcjd.v18.i33.3594 ◽

2010 ◽

Vol 18 (33) ◽

pp. 3594

Author(s):

Sheng-Qin Zheng ◽

Jie He ◽

Pei-Lin Huang ◽

Jian-Hua Wang

Keyword(s):

Colorectal Cancer ◽

Protein Expression ◽

Clinical Significance ◽

Human Colorectal Cancer

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Dehydroepiandrosterone Administration or Gαq Overexpression Induces β-Catenin/T-Cell Factor Signaling and Growth via Increasing Association of Estrogen Receptor-β/Dishevelled2 in Androgen-Independent Prostate Cancer Cells

Endocrinology ◽

10.1210/en.2009-0885 ◽

2010 ◽

Vol 151 (4) ◽

pp. 1428-1440 ◽

Cited By ~ 11

Author(s):

Xunxian Liu ◽

Julia T. Arnold ◽

Marc R. Blackman

Keyword(s):

Prostate Cancer ◽

Estrogen Receptor ◽

T Cell ◽

Cell Growth ◽

Protein Expression ◽

Cyclin D1 ◽

D1 Protein ◽

Nutritional Supplement ◽

T Cell Factor ◽

Androgen Independent

β-Catenin/T-cell factor signaling (β-CTS) plays multiple critical roles in carcinogenesis and is blocked by androgens in androgen receptor (AR)-responsive prostate cancer (PrCa) cells, primarily via AR sequestration of β-catenin from T-cell factor. Dehydroepiandrosterone (DHEA), often used as an over-the-counter nutritional supplement, is metabolized to androgens and estrogens in humans. The efficacy and safety of unregulated use of DHEA are unclear. We now report that DHEA induces β-CTS via increasing association of estrogen receptor (ER)-β with Dishevelled2 (Dvl2) in AR nonresponsive human PrCa DU145 cells, a line of androgen-independent PrCa (AiPC) cells. The induction is temporal, as assessed by measuring kinetics of the association of ERβ/Dvl2, protein expression of the β-CTS targeted genes, c-Myc and cyclin D1, and cell growth. However, in PC-3 cells, another human AiPC cell line, DHEA exerts no detectible effects, partly due to their lower expression of Gα-subunits and DHEA down-regulation of ERβ/Dvl2 association. When Gαq is overexpressed in PC-3 cells, β-CTS is constitutively induced, including increasing c-Myc and cyclin D1 protein expression. This effect involved increasing associations of Gαq/Dvl2 and ERβ/Dvl2 and promoted cell growth. These activities require ERβ in DU-145 and PC-3 cells because they are blocked by ICI 182–780 treatment inactivating ERβ, small interfering RNA administration depleting ERβ, or AR overexpression arresting ERβ. These data suggest that novel pathways activating β-CTS play roles in the progression of AiPC. Although DHEA may enhance PrCa cell growth via androgenic or estrogenic pathways, the effects of DHEA administration on clinical prostate function remain to be determined.

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Red Raspberry Extracts Inhibit A549 Lung Cancer Cell Migration, Invasion, and Epithelial-Mesenchymal Transition Through the Epidermal Growth Factor Receptor/Signal Transducer and Activator of Transcription-3 Signaling Pathway

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2506 ◽

2021 ◽

Vol 11 (3) ◽

pp. 439-444

Author(s):

Jiayi Ren ◽

Lifang Wang ◽

Jia Fu ◽

Chunyang Wang ◽

Yan Gong ◽

...

Keyword(s):

Lung Cancer ◽

Protein Expression ◽

Cyclin D1 ◽

Signaling Pathway ◽

A549 Cells ◽

Advanced Lung Cancer ◽

Migration And Invasion ◽

Red Raspberry ◽

A549 Lung ◽

E Cadherin

The incidence and mortality of lung cancer ranks first among all malignant tumors in the world. Because it is relatively asymptomatic at early stages, most patients do not become aware of the disease until it has progressed to an advanced stage. Advanced lung cancer metastasis results in systemic cachexia and effective treatment becomes challenging, leading to poor response and outcome. Therefore, the development of new drugs for the treatment of lung cancer is paramount. In this study, A549 cells were treated with different concentrations of red raspberry extract and the proliferation, migration, and invasion of cells were evaluated. The results indicated that red raspberry extract reduced the proliferation, migration, and invasion of A549 cells. Western blot analysis was used to detect the expression of the cyclin D1, N-cadherin, vimentin, E-cadherin, EGFR, and STAT3 proteins. Treatment with red raspberry extract reduced the expression of cyclin D1, N-cadherin, vimentin, EGFR, and STAT3, whereas the expression of E-cadherin increased. Following transfection of an EGFR overexpression vector into A549 cells, we observed a reduced inhibitory effect of the red raspberry extract on the proliferation, migration, and invasion of A549 cells. In addition, EGFR overexpression abrogated the increased expression of cyclin D1, N-cadherin, vimentin, EGFR, and STAT3 protein expression in A549 cells following extract treatment. In contrast, E-cadherin protein expression was decreased under these treatment conditions. Overall, this study suggests that red raspberry extract may reduce the proliferation, migration, invasion, and epithelialmesenchymal transition of A549 lung cancer cells by inhibiting the activation of the EGFR/STAT3 signaling pathway. These findings may lead to the development of new strategies to treat advanced lung cancer.

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The expression and clinical significance of PDCD4 and Her-2 in human gastric cancer

European Journal of Inflammation ◽

10.1177/2058739219828236 ◽

2019 ◽

Vol 17 ◽

pp. 205873921982823

Author(s):

Yuelou Yang ◽

Xiangjun Jiang ◽

Dong Li ◽

Feiyan Wang ◽

Qun Yang ◽

...

Keyword(s):

Gastric Cancer ◽

Protein Expression ◽

Western Blot ◽

Clinical Significance ◽

Normal Mucosa ◽

Normal Tissues ◽

Positive Rate ◽

Her 2 ◽

Cancer Tissues ◽

Pdcd4 Protein

To investigate the correlation and clinical significance between programmed cell death factor 4 (PDCD4) and epidermal growth factor receptor 2 (Her-2) expressions and clinicopathological parameters in patients with gastric cancer, a total of 65 cases of gastric cancer and the corresponding normal mucosa with PDCD4 and Her-2 protein expressions were detected by SP immunohistochemical staining, and 50 cases of gastric cancer and the corresponding normal mucosa with PDCD4 and Her-2 protein expression quantities were detected by Western blot, in order to analyze the relationship between the positive expressions of PDCD4 and Her-2 protein and the clinicopathological features of patients with gastric cancer. The results showed that the positive rate of PDCD4 protein expression in gastric cancer tissues was 7.7%, which was significantly lower than that in the corresponding normal tissues, that is, 77.5% ( P < 0.05); the positive rate of Her-2 expression was 41.5%, which was significantly higher than that of the corresponding normal tissues, which is 2.5% ( P < 0.05). The Western blot test showed that the expression of PDCD4 protein in gastric cancer was 0.3105 ± 0.0073, which was significantly lower than that in the corresponding normal tissues, that is, 0.9428 ± 0.0127 ( P < 0.05); the expression level of Her-2 protein in gastric cancer tissues was 0.9428 ± 0.0127, which was significantly higher than that of the corresponding normal mucosa, which is 0.2054 ± 0.0264 ( P < 0.05). The positive expressions of PDCD4 (5/65) and Her-2 (27/65) were significantly correlated with the differentiation degrees and TNM stages of gastric cancer ( P < 0.05). However, no significant correlation can be observed from Table 2 ( P > 0.05), regarding sex, age, tumor size, and lymph node metastasis. Our research claimed that PDCD4 and Her-2 may play an important role in the invasion and metastasis of gastric cancer, which has a negative correlation with biological behaviors of gastric cancer. The low expression of PDCD4 and the high expression of Her-2 in gastric cancer may promote the occurrence and progression of cancer. The PDCD4 and Her-2 test can be used as an index to evaluate the malignant biological behaviors of gastric cancer and prognosis, and provide a theoretical basis for targeted therapy.

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