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

Chai, San Jiun; Zabidi, Muhammad Mamduh Ahmad; Gan, Siew Pey; Rajadurai, Pathmanathan; Lim, Paul Vey Hong; Ng, Ching Ching; Yap, Lee Fah; Teo, Soo‐Hwang; Lim, Ka Keat; Patel, Vyomesh; Cheong, Sok Ching

doi:10.1155/2019/3857853

Cited by 13 publications

(11 citation statements)

References 55 publications

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“…18 Although the exact biological function of FJX1 in human cancers remains unclear, studies of different species indicate that FJX1 participates in carcinogenesis and FJX1 gene amplification as well as subsequent mRNA expression have been found, besides, FJX1 has also been considered as a candidate for regulation of angiogenesis in several human cancers, including CRC. [19][20][21] However, whether specific crosstalk existed between PVT1 and FJX1 through competition for miR-106b-5p binding in CRC is unclear.…”

Section: Introductionmentioning

confidence: 99%

<p>Knockdown of PVT1 Suppresses Colorectal Cancer Progression by Regulating MiR-106b-5p/FJX1 Axis</p>

Liu¹,

Wu²,

Guan³

et al. 2020

CMAR

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Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) has been revealed to involve in the progression of CRC. However, the precise mechanisms of PVT1 in action remain unclear. Methods: The expression of PVT1, microRNA-106b-5p (miR-106b-5p) and four jointed box 1 (FJX1) was measured using quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot, respectively. Cell proliferation was investigated by 3-(4,5)dimethylthiahiazo (−z-y1)-3,5-di-phenytetrazoliumromide assay. Transwell assay was used to determine cell migration and invasion. The correlation between miR-106b-5p and PVT1 or FJX1 was confirmed using luciferase reporter assay. The effects of PVT1 in vivo were assessed using mice xenograft model. Results: PVT1 was up-regulated in CRC tissues and cell lines, especially in CRC tissues with high-grade, and highly expressed PVT1 predicted worse prognosis. Functional experiments demonstrated that PVT1 deletion inhibited CRC cell proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. MiR-106b-5p was confirmed to be a target of PVT1, and inhibition of miR-106b-5p reversed the inhibitory effects of PVT1 knockdown on CRC cell malignant phenotypes. In addition, we found miR-106b-5p directly targeted FJX1, and miR-106b-5p-mediated inhibition on CRC cell proliferation, migration and invasion was attenuated by FJX1 up-regulation. Importantly, it was also proved that PVT1 could indirectly regulate FJX1 expression via targeting miR-106b-5p. Conclusion: Knockdown of PVT1 impaired cell proliferation, migration and invasion in CRCs via regulating miR-106b-5p/FJX1 axis, which provided a novel insight into the development of therapeutic strategies for CRC patients.

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Section: Introductionmentioning

confidence: 99%

<p>Knockdown of PVT1 Suppresses Colorectal Cancer Progression by Regulating MiR-106b-5p/FJX1 Axis</p>

Liu¹,

Wu²,

Guan³

et al. 2020

CMAR

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“…Microarrays and WES have facilitated the identification of several candidate biomarkers such as FJX, WNT5A, CLDN1, FGFR3, FZD6, and SOX4. Among these genes, it was reported that the four-jointed box 1 (FJX1) is overexpressed in NPC tissues and promotes cell proliferation through regulating Cycline D1 and E1 [ 32 ]. Furthermore, several key signaling pathways such as Notch, NF- κ B, and PI3K/Akt were frequently altered during NPC development and progression [ 26 , 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

FOXA1 Expression in Nasopharyngeal Carcinoma: Association with Clinicopathological Characteristics and EMT Markers

Ammous-Boukhris

Ayadi

Derbel

et al. 2020

BioMed Research International

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The forkhead box (FOXA) family of transcription factors regulates gene expression and chromatin structure during tumorigenesis and embryonic development. Until now, the relationship between FOXA1 and the nasopharyngeal carcinoma (NPC) has not yet been reported. Therefore, our purpose is to analyze the expression of FOXA1 in 56 NPC patients compared to 10 normal nasopharyngeal mucosae and to correlate the expression with the clinicopathological features. Besides, we investigated the association between FOXA1 and LMP1 gene expression, as well as the EMT markers namely the E-cadherin and Twist1. Among 56 NPC tissues, 34 (60.7%) cases were positive for FOXA1. Furthermore, we noticed that FOXA1 expression correlated with TNM (p=0.037), and age at diagnosis (p=0.05). Moreover, positive expression of FOXA1 is likely to be associated with prolonged disease-free survival and overall survival rates. On the other hand, we observed a positive association between the expression of E-cadherin and FOXA1 (p=0.0051) whereas Twist1 correlated negatively with FOXA1 (p=0.004). Furthermore, knowing that LMP1 plays a key role in the pathogenesis of NPC, we explored the association of FOXA1 with the LMP1 gene expression in both NPC cell lines and tissues. We found that, in the C666-1 which displays low levels of LMP1, the expression of FOXA1 is high, and inversely in the C15 cell line that expresses a high level of LMP1, the level of FOXA1 is low. Besides, in accordance to our results, we found that in NPC tissues there is a negative association between LMP1 and FOXA1. In conclusion, our results suggest that the overexpression of FOXA1 is associated with a nonaggressive behavior and favorable prognosis in NPC patients. FOXA1 could contribute in the EMT process through key factors as E-cadherin, Twist1, and LMP1.

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“…As alluded to in the introduction, the study of extracellular kinases was spearheaded by Ken Irvine’s laboratory when they published the first example of a secreted kinase, the fly protein Fj, which they went on to show phosphorylated unusual cadherin domains ( 12 ). The murine equivalent of Fj, four-jointed box 1 (FJX1) is involved in forming appropriate dendrite arbor morphology in the hippocampus ( 24 ), and recently, human FJX1 has been shown to increase the invasive potential of nasopharyngeal cancer cells ( 25 , 26 ). In addition to FJX1 and Fam20A, B, and C, this small family contains two additional members, Fam198A and Fam198B.…”

Section: Secreted Kinasesmentioning

confidence: 99%

The ABCs of the atypical Fam20 secretory pathway kinases

Worby

Mayfield

Pollak

et al. 2021

Journal of Biological Chemistry

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The study of extracellular phosphorylation was initiated in late 19th century when the secreted milk protein, casein, and egg-yolk protein, phosvitin, were shown to be phosphorylated. However, it took more than a century to identify Fam20C, which phosphorylates both casein and phosvitin under physiological conditions. This kinase, along with its family members Fam20A and Fam20B, defined a new family with altered amino acid sequences highly atypical from the canonical 540 kinases comprising the kinome. Fam20B is a glycan kinase that phosphorylates xylose residues and triggers peptidoglycan biosynthesis, a role conserved from sponges to human. The protein kinase, Fam20C, conserved from nematodes to humans, phosphorylates well over 100 substrates in the secretory pathway with overall functions postulated to encompass endoplasmic reticulum homeostasis, nutrition, cardiac function, coagulation, and biomineralization. The preferred phosphorylation motif of Fam20C is SxE/pS, and structural studies revealed that related member Fam20A allosterically activates Fam20C by forming a heterodimeric/tetrameric complex. Fam20A, a pseudokinase, is observed only in vertebrates. Loss-of-function genetic alterations in the Fam20 family lead to human diseases such as amelogenesis imperfecta, nephrocalcinosis, lethal and nonlethal forms of Raine syndrome with major skeletal defects, and altered phosphate homeostasis. Together, these three members of the Fam20 family modulate a diverse network of secretory pathway components playing crucial roles in health and disease. The overarching theme of this review is to highlight the progress that has been made in the emerging field of extracellular phosphorylation and the key roles secretory pathway kinases play in an ever-expanding number of cellular processes.

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

Cited by 13 publications

References 55 publications

<p>Knockdown of PVT1 Suppresses Colorectal Cancer Progression by Regulating MiR-106b-5p/FJX1 Axis</p>

<p>Knockdown of PVT1 Suppresses Colorectal Cancer Progression by Regulating MiR-106b-5p/FJX1 Axis</p>

FOXA1 Expression in Nasopharyngeal Carcinoma: Association with Clinicopathological Characteristics and EMT Markers

The ABCs of the atypical Fam20 secretory pathway kinases

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