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Fulltext An Oncogenic Role for Four-Jointed Box 1 (FJX1) in Nasopharyngeal Carcinoma

Chai SJ, Ahmad Zabidi MM, Gan SP, Rajadurai P, Lim PVH, Ng CC, et al.

Dis Markers, 2019;2019:3857853.
PMID: 31236144 DOI: 10.1155/2019/3857853

Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer prevalent in Southern China and Southeast Asia. The current knowledge on the molecular pathogenesis of NPC is still inadequate to improve disease management. Using gene expression microarrays, we have identified the four-jointed box 1 (FJX1) gene to be upregulated in primary NPC tissues relative to nonmalignant tissues. An orthologue of human FJX1, the four-jointed (fj) gene in Drosophila and Fjx1 in mouse, has reported to be associated with cancer progression pathways. However, the exact function of FJX1 in human is not well characterized. The overexpression of FJX1 mRNA was validated in primary NPC tissue samples, and the level of FJX1 protein was significantly higher in a subset of NPC tissues (42%) compared to the normal epithelium, where no expression of FJX1 was observed (p = 0.01). FJX1 is also found to be overexpressed in microarray datasets and TCGA datasets of other cancers including head and neck cancer, colorectal, and ovarian cancer. Both siRNA knockdown and overexpression experiments in NPC cell lines showed that FJX1 promotes cell proliferation, anchorage-dependent growth, and cellular invasion. Cyclin D1 and E1 mRNA levels were increased following FJX1 expression indicating that FJX1 enhances proliferation by regulating key proteins governing the cell cycle. Our data suggest that the overexpression of FJX1 contributes to a more aggressive phenotype of NPC cells and further investigations into FJX1 as a potential therapeutic target for NPC are warranted. The evaluation of FJX1 as an immunotherapy target for NPC and other cancers is currently ongoing.

Matched MeSH terms: Cyclins/genetics; Cyclins/metabolism
Phyla nodiflora L. Extracts Induce Apoptosis and Cell Cycle Arrest in Human Breast Cancer Cell Line, MCF-7

Teoh PL, Liau M, Cheong BE

Nutr Cancer, 2019;71(4):668-675.
PMID: 30663402 DOI: 10.1080/01635581.2018.1559942

Phyla nodiflora L. has been used as medicinal remedies for various ailments due to its antioxidant, anti-inflammatory, anti-bacterial, anti-tumor activity. Previously, we found that the plant extracts induced DNA fragmentation in MCF-7. This study was to investigate the modes of action of P. nodiflora in inhibiting breast cancer cells using leaf ethyl acetate (EA leaf), stem ethyl acetate (EA stem) and stem methanol (Met stem) extracts. The MTT assay showed that the anti-proliferative effects of P. nodiflora extracts were selective towards MCF-7 with a minimal effect on MCF10A. Morphological changes such as cell shrinkage and nuclear condensation were observed in treated cells. We found that induction of apoptosis by EA leaf and EA stem was mitochondrial-dependent while loss of mitochondrial membrane potential was not found in Met stem-treated cells. In addition, the expression levels of AIFM1, CASP9, CFLAR, and IGF1R were altered after treatment. Decreased BCL-2 expression was found in treated cells while BAX and caspases' expression was upregulated or maintained. All extracts caused perturbation of cell cycle at S phase by dysregulating the expression of cell cycle regulators such as CDKs and cyclins. Our findings indicate that P. nodiflora inhibits MCF-7 cells by inducing apoptosis and perturbing cell cycle.

Matched MeSH terms: Cyclins
Fulltext Mesenchymal stem cells: a modern tool for immunomodulation

Rajesh Ramasamy

Malaysian Journal of Medicine and Health Sciences, 2019;15(108):13-13.
MyJurnal

Immunomodulation is essential for controlling the immune system to maintain efficient immune surveillance and inflammation. Both arms of immunomodulation, namely immunostimulation and immunosuppression, are equally crucial in setting the optimal balance of immune response. However, diseases or conditions such as autoimmune diseases, tissue rejection due to transplantation and chronic inflammation require downregulation of overwhelming immune reactions. The conventional immunosuppressive drugs prevent the activation of immune cells, yet create an unsafe condition with toxic adverse effects. In such predicament, mesenchymal stem cells (MSCs) emerged as one of the safe immunosuppressive regiments and widely tested in clinical trials for numerous chronic inflammatory dis-eases. Mesenchymal stem cells are the origin of the stromal/mesenchymal cells in almost all solid organs, including the pulp of the tooth. In addition to providing structural support to the organ, MSCs participate in the tissue repair and regeneration by ameliorating an overly activated immune response locally and systemically. Regardless of the source, MSCs profoundly suppress the proliferation and effector functions of both innate and adaptive immune cells. The mechanism of inhibition primarily took place in the early phase of cell cycle and mediated via suppression of mainstream signalling pathways that involve cyclins and other cell cycle proteins. The antiproliferative activity of MSCs is not only limited to the healthy immune cells but extends to the various tumour cells of the immune system. Similarly, an array of cell signalling pathways that executed by cell cycle proteins found downregulated in the pres-ence of MSCs. The immunosuppressive activity exerted by MSCs is not specific to particular immune cells where it impairs a group of the common cell signalling pathways or putative cell cycle proteins which are vital elements for the proliferation.

Matched MeSH terms: Cyclins
Fulltext Regulation of Plasmodium falciparum cell cycle involving cyclins and cyclin dependent kinases

Siti Nurfatimah Mohd Shahpudin, Doblin Anak Sandai, Sharlina Mohamad

Malaysian Journal of Medicine and Health Sciences, 2020;16(102):60-67.
MyJurnal

Protein kinases (PKs) are regulators of protein phosphorylation in many infectious diseases, including malaria. How- ever, the cellular functions of majority of PKs in Plasmodium falciparum remain unknown. The mechanisms involved in P. falciparum cell cycle progress are not fully understood. The activation of cyclin-dependent kinases (CDKs), which constitute a PK family that includes crucial regulators of cell cycle progression in eukaryotes, is strictly being coordinated by the interaction with specific cyclins at well-defined points within the cell cycle. These cyclin/CDK complexes are very well characterised in humans, but little is known in P. falciparum. This review expand our un- derstanding of the characteristic of CDKs and cyclins in P. falciparum, and paves the way for further investigations on the precise molecular role of these crucial regulatory proteins in mosquito and human. This represents a valuable step towards the elucidation of cell cycle control mechanisms in malaria parasites.

Matched MeSH terms: Cyclins
A comparative study of the expression of Wnt-1, WISP-1, survivin and cyclin-D1 in colorectal carcinoma

Khor TO, Gul YA, Ithnin H, Seow HF

Int J Colorectal Dis, 2006 May;21(4):291-300.
PMID: 16041507

BACKGROUND AND AIMS: It is well accepted that activation of Wnt signalling occurs in colorectal carcinoma (CRC), but the correlation amongst the various proteins involved in primary tumours are still unclear. The expression of the inducer of this pathway, Wnt-1, and the downstream effectors, WISP-1, cyclin-D1 and survivin proteins, was compared in a series of CRC tissues with the apparently normal adjacent tissues to determine the relationship of these proteins.
PATIENTS AND METHODS: Formalin-fixed, paraffin-embedded tissue samples of 47 CRCs surgically resected at the Kuala Lumpur Hospital (KLH) between 1999 and 2000 were used. Immunohistochemical staining with monoclonal antibodies against cyclin-D1 and survivin and polyclonal antibodies against Wnt-1 and WISP-1 was performed. Results of immunohistochemistry were analysed for correlation between biomolecules and histopathological data of the patients.
RESULTS: Of the 47 CRCs, 26 (55.3%), 15 (31.9%), 5 (10.6%) and 28 (59.6%) of the tumours exhibited positivity for Wnt-1, WISP-1, cyclin D1 and survivin, respectively. A lower percentage of the 40 apparently normal adjacent tissues were found to be positive for Wnt-1 (7, 17.5%), WISP-1 (+/-5, 12.5%) and survivin (13, 32.5%), but cyclin D1 was not detected in any of them. Interestingly, the total scores of Wnt-1, WISP-1 and survivin were significantly higher in CRC tissues (p=0.001, 0.034 and 0.044, respectively). Using the Spearman rank correlation test, a positive linear relationship was found between total Wnt-1 score with total WISP-1 score (rho=0.319, p=0.003) and total survivin score (rho=0.609, p=or<0.001). The expression of WISP-1 in the CRC tissues was found to be positively correlated with patients older than 60 years old (p=0.011). In addition, nuclear cyclin-D1 expression was found to be associated with poorly differentiated CRC tissues (p<0.001, Table 5) and right-sided CRC tumour (p=0.019, Table 6). Total WISP-1 score was associated with well-differentiated CRC tissues (p=0.029).
CONCLUSIONS: Overexpression and interplay between Wnt-1, WISP-1, survivin and cyclin-D1 may play a role in tumorigenesis, possibly by promoting cell cycle checkpoint progression, accelerating cell growth and inhibiting apoptosis. Our data may provide useful information towards the search for potent therapeutic targets towards the development of novel treatment strategies for CRC.

Matched MeSH terms: Cyclins/metabolism*
Fulltext Chemopreventive effects of pterostilbene through p53 and cell cycle in mouse lung of squamous cell carcinoma model

Surien O, Ghazali AR, Masre SF

Sci Rep, 2021 Jul 21;11(1):14862.
PMID: 34290382 DOI: 10.1038/s41598-021-94508-7

Cell proliferation and cell death abnormalities are strongly linked to the development of cancer, including lung cancer. The purpose of this study was to investigate the effect of pterostilbene on cell proliferation and cell death via cell cycle arrest during the transition from G1 to S phase and the p53 pathway. A total of 24 female Balb/C mice were randomly categorized into four groups (n = 6): N-nitroso-tris-chloroethyl urea (NTCU) induced SCC of the lungs, vehicle control, low dose of 10 mg/kg PS + NTCU (PS10), and high dose of 50 mg/kg PS + NTCU (PS50). At week 26, all lungs were harvested for immunohistochemistry and Western blotting analysis. Ki-67 expression is significantly lower, while caspase-3 expression is significantly higher in PS10 and PS50 as compared to the NTCU (p

Matched MeSH terms: Cyclins/genetics; Cyclins/metabolism