Jan-Jong Hung

National Cheng Kung University | NCKU · Institute of Biotechnology and Bioindustry Sciences

Tumor heterogeneity is the major factor for inducing drug resistance. p53 is the major defender to maintain genomic stability, which is a high proportion mutated in most of the cancer types. In this study, we established in vivo animal models of gefitinib-induced drug-resistant lung cancer containing EGFRL858R and EGFRL858R*Tp53+/- mice to explore...

Previous studies indicate that estrogen positively regulates lung cancer progression. Understanding the reasons will be beneficial for treating women with lung cancer in the future. In this study, we found that tumor formation was more significant in female EGFRL858R mice than in male mice. P53 expression levels were downregulated in the estradiol...

Background Sp1, an important transcription factor, is involved in the progression of various cancers. Our previous studies have indicated that Sp1 levels are increased in the early stage of lung cancer progression but decrease during the late stage, leading to poor prognosis. In addition, estrogen has been shown to be involved in lung cancer progre...

Drug resistance has remained an important issue in the treatment and prevention of various diseases, including cancer. Herein, we found that USP24 not only repressed DNA-damage repair (DDR) activity by decreasing Rad51 expression to cause the tumor genomic instability and cancer stemness, but also increased the levels of the ATP-binding cassette (A...

Bromodomain (BRD)-containing proteins are important for chromatin remodeling to regulate gene expression. In this study, we found that the deubiquitinase USP24 interacted with BRD through its C-terminus increased the levels of most BRD-containing proteins through increasing their protein stability by the removal of ubiquitin from Lys391/Lys400 of t...

In this study, we found that Sp1 was highly expressed in astrocytes, implying that Sp1 might be important for the function of astrocytes. Sp1/GFAP-Cre-ERT2 conditional knockout mice were constructed to study the role of Sp1 in astrocytes. Knockout of Sp1 in astrocytes altered astrocytic morphology and decreased GFAP expression in the cortex and hip...

Protein ubiquitination is an important mechanism for regulating the activity and levels of proteins under physiological conditions. Loss of regulation by protein ubiquitination leads to various diseases, such as cancer. Two types of enzymes, namely, E1/E2/E3 ligases and deubiquitinases, are responsible for controlling protein ubiquitination. The ub...

[This corrects the article DOI: 10.18632/oncotarget.3701.].

Lung cancer is a malignant lung tumor characterized by high incidence and motility. c-Myc is a transcription factor that plays an important role in oncogenic activation to influence cellular metabolism and proliferation. Ubiquitin-specific peptidase 24 (USP24) is one of the members of USPs family to regulate protein ubiquitination. However, it is l...

Lung cancer is a malignant lung tumor characterized by high incidence and motility. c-Myc is a transcription factor that plays an important role in oncogenic activation to influence cellular metabolism and proliferation. Ubiquitin-specific peptidase 24 (USP24) is one of the members of USPs family to regulate protein ubiquitination. However, it is l...

Ubiquitin‐specific peptidases (USPs), belong to a large family of cysteine proteases, and are deubiquitinases (DUBs) that specifically recognize and remove ubiquitin molecules from proteins. Previously, we discovered ubiquitin‐specific peptidase 24 (USP24) was upregulated in late stage lung cancer patients due to its genomic variants caused by sing...

Sp1 as a transcriptional factor regulates many genes related to various physiological conditions such as cellular survival, death, and development, and it also involves in many diseases such as cancer. In the past, we found that Sp1 could be up regulation through H 2 O 2 ‐mediated IRES‐dependent translational pathway to protect neuron from ischemic...

Homologous recombination is a type of genetic recombination in which nucleotide sequences are exchanged between two similar or identical molecules of DNA. It is most widely used by cells to accurately repair harmful breaks that occur on both strands of DNA, known as double‐strand breaks. Ubiquitin‐specific peptidases (USPs) belong to a large family...

We have previously demonstrated that USP24 is involved in cancer progression. Here, we found that USP24 expression is upregulated in M2 macrophages and lung cancer cells. Conditioned medium from USP24-knockdown M2 macrophages decreases the migratory and chemotactic activity of lung cancer cells and the angiogenic properties of human microvascular e...

Our previous study indicated that increase in USP24 level in lung cancer facilitates lung cancer metastasis. Our recent study found that higher USP24 level was found in tumor‐associated microenvironment (TAM) than surrounding lung cancer cells in lung cancer patient specimens. USP24 level was significantly increased in M2‐macrophages. Knockdown of...

Lung cancer is the leading cause of cancer mortality worldwide. In particular,tumor metastasis is the most life-threatening event of lung cancer patients. More and more effective drugs for clinical use in cancer therapy have been developed up to now. However,the drug resistance is always occurred after drug treatment for a long time. Therefore,how...

Our recent studies have indicated that specificity protein-1 (Sp1) accumulates substantially in the early stage of lung cancer but is partially decreased in the late stages, which is an important factor in the progression of the cancer. In this study, we found that Nm23-H1 and hnRNPA2/B1 could be recruited to the 5′UTR of Sp1 mRNA. In investigating...

Acquisition of temozolomide (TMZ) resistance is a major factor leading to the failure of glioblastoma (GBM) treatment. The exact mechanism by which GBM evades TMZ toxicity is not always related to the expression of the DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT), and so remains unclear. In this study, TMZ-resistant variants de...

The Fanconi anemia pathway in coordination with homologous recombination is essential to repair interstrand crosslinks (ICLs) caused by cisplatin. TIP60 belongs to the MYST family of acetyltransferases and is involved in DNA repair and regulation of gene transcription. Although the physical interaction between the TIP60 and FANCD2 proteins has been...

Steroidogenesis-mediated production of neurosteroids is important for brain homeostasis. Cytochrome P450 17A1 (CYP17A1), which converts pregnenolone to dehydroepiandrosterone (DHEA) in endocrine organs and the brain, is required for prostate cancer progression and acquired chemotherapeutic resistance. However, whether CYP17A1-mediated DHEA synthesi...

Steroidogenesis-mediated production of neurosteroids is important for brain homeostasis. Cytochrome P450 17A1 (CYP17A1), which converts pregnenolone to dehydroepiandrosterone (DHEA) in endocrine organs and the brain, is required for prostate cancer progression and acquired chemotherapeutic resistance. However, whether CYP17A1-mediated DHEA synthesi...

In this study, several cancer-related proteins (Bax, p300, E2F4 and securin) have been proven to be substrates of ubiquitin-specific peptidase 24 (USP24), and relevance has been shown between USP24 and its substrates in samples from clinical lung cancer patients. Silencing USP24 increases the cancer formation by inhibiting cellular apoptosis and in...

The role of IL10 in the tumorigenesis of various cancer types is still controversial. Here, we found that increased IL10 levels are correlated with a poor prognosis in lung cancer patients. Moreover, IL10 levels were significantly increased in the lungs and serum of EGFRL858R- and Kras4bG12D-induced lung cancer mice, indicating that IL10 might faci...

T-cell lymphoma invasion and metastasis 2 (TIAM2) is a neuron-specific protein that has been found ectopically expressed in hepatocellular carcinoma (HCC). Results from clinical specimens and cellular and animal models have shown that the short form of TIAM2 (TIAM2S) functions as an oncogene in the tumorigenesis of liver cancer. However, the regula...

The accumulation of reactive oxygen species (ROS) have implicated the pathogenesis of several human diseases including neurodegenerative disorders, stroke, and traumatic brain injury, hence protecting neurons against ROS is very important. In this study, we focused on sigma-1 receptor (Sig-1R), a chaperone at endoplasmic reticulum, and investigated...

Ubiquitin is a critical modifier regulating the degradation and function of its target proteins during posttranslational modification. Here we found that ubiquitin-specific peptidase 24 (USP24) is highly expressed in cell lines with enhanced malignancy and in late-stage lung cancer clinical samples. Studying single-nucleotide polymorphisms (SNPs) o...

DNA double strand breaks (DSBs) represent one of the most threatening lesions to the integrity of genomes. In yeast Saccharomyces cerevisiae, NuA4, a histone acetylation complex, is recruited to DSBs, wherein it acetylates histones H2A and H4, presumably relaxing the chromatin and allowing access to repair proteins. Two subunits of NuA4, Yng2 and E...

Significance The endoplasmic reticulum (ER), although functioning as protein synthesis machinery in the cell, plays other important roles that have yet to be fully unveiled. We found here that the ER can directly send an envoy protein, the sigma-1 receptor (Sig-1R), to the nuclear envelope (NE), where the Sig-1R begins to recruit chromatin-remodeli...

Ubiquitin‐specific protease (USP) 24 is one of deubiquinating enzymes (DUBs), which remove polyubiquitin chains from protein substrates and thereby prevent the substrates from ubiquitin‐mediated proteasomal degradation. However, little is so far known about the possible role of USP24 in control of protein deubiquitination or in physiological functi...

We previously showed that Sp1 phosphorylation at Thr739 decreases its DNA binding activity. In this study, we found that phosphorylation of Sp1 at Thr739 alone is necessary, but not essential for the inhibition of its DNA binding activity during mitosis. Further study showed that Pin1 could be recruited to the Thr739(p)‐Pro motif of Sp1 to modulate...

Herein, we evaluated the anti-cancer effect and molecular mechanisms of a novel betulinic acid (BA) derivative, SYK023, by using two mouse models of lung cancer driven by KrasG12D or EGFRL858R. We found that SYK023 inhibits lung tumor proliferation, without side effects in vivo or cytotoxicity in primary lung cells in vitro. SYK023 triggered endopl...

We have shown that Sp1 phosphorylation at Thr739 decreases its DNA-binding activity. In this study, we found that phosphorylation of Sp1 at Thr739 alone is necessary, but not sufficient for the inhibition of its DNA-binding activity during mitosis. We demonstrated that Pin1 could be recruited to the Thr739(p)-Pro motif of Sp1 to modulate the intera...

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Nucleolin, expressed in various cellular compartments, participates in DNA transcription, ribosomal biogenesis, regulation of RNA stability. It is evidence that the posttranslational cleavage of nucleolin determine the fate of cells, apoptosis or proliferation. However, the cont...

Aberrant activation of signal transducer and activator of transcription 3 (Stat3) occurs in many cancers and plays a critical role in tumor progression. The system that Stat3-induced Sphingosine-1-phosphate receptor 1 (S1PR1) expression and the S1P-S1PR1 pathway reciprocally regulate Stat3 activity was considered a major positive feedback loop for...

Our previous study indicated that specificity protein-1 (Sp1) is accumulated during hypoxia in an internal ribosomal entry site (IRES)-dependent manner. Herein, we found that the Sp1 was induced strongly at the protein level, but not in the mRNA level, in lung tumor tissue, indicating that translational regulation might contribute to the Sp1 accumu...

Mutant Kras (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) is observed in more than 20% of non-small-cell lung cancers; however, no effective Kras target therapy is available at present. The Kras DNA vaccine may represent as a novel immunotherapeutic agent in lung cancer. In this study, we investigated the antitumor efficacy of the Kras DNA...

Cisplatin can cause intrastrand and interstrand crosslinks between purine bases and is a chemotherapeutic drug widely used to treat cancer. However, the major barrier to the efficacy of the treatment is drug resistance. Homologous recombination (HR) plays a central role in restoring stalled forks caused by DNA lesions. Here, we report that chronic...

P300 is a transcription cofactor for a number of nuclear proteins. Most studies of p300 have focused on the regulation of its function, which primarily includes its role as a transcription co-factor for a number of nuclear proteins. In this study, we found that p300 was highly phosphorylated and its level was decreased during mitosis and tumorigene...

Nucleolin (NCL) participates in DNA transcription, ribosomal biogenesis and the regulation of RNA stability. However, the contribution of NCL to tumor development is still not clear. Herein, we found that NCL expression correlated with poor prognosis in lung cancer patients. Overexpressed NCL was predominantly cleaved to C-terminal truncated NCL (T...

Our recent study indicated that overexpression of Sp1 enhances the proliferation of lung cancer cells, while represses metastasis. In this study, we found that the transcriptional activity of FOXO3 was increased, but its protein levels decreased following Sp1 expression. Sp1 increased expression of miR-182, which was then recruited to the 3'-untran...

58-kDa microspherule protein (MSP58) plays an important role in a variety of cellular processes including transcriptional regulation, cell proliferation and oncogenic transformation. Currently, the mechanisms underlying the oncogenic effect of MSP58 are not fully understood. The human telomerase reverse transcriptase (hTERT) gene, which encodes an...

Alcoholism induces folate deficiency and increases the risk for embryonic anomalies. However, the interplay between ethanol exposure and embryonic folate status remains unclear. To investigate how ethanol exposure affects embryonic folate status and one-carbon homeostasis, we incubated zebrafish embryos in ethanol and analyzed embryonic folate cont...

Sp1 is a transcriptional factor to regulate numbers genes related to cell proliferation, apoptosis and tumor progression. Previous studies indicate that Sp1 is induced significantly through modulating its transcriptional activity and protein stability. To detail study the level of Sp1 protein and mRNA in tumorigenesis found that Sp1 mRNA was just i...

Sp1 as a transcriptional factor regulates its target genes involved in cell growth, differentiation and apoptosis. Our previous study indicates that Sp1 accumulation is critical for lung tumorigenesis. Several microRNAs are also reported to be involved in cancer formation. Is there any relationship between Sp1 and mirRNA in lung tumorigenesis ? To...

Specific protein 1 (Sp1), the first transcription factor to be isolated, regulates the expression of numerous genes involved in cell proliferation, apoptosis, and differentiation. Recent studies found that an increase in Sp1 transcriptional activity is associated with the tumorigenesis. Moreover, post-translational modifications of Sp1, including g...

Previous studies have shown that the inhibitory effect of betulinic acid (BA) on specificity protein (Sp1) expression is involved in the prevention of cancer progression, but the mechanism of this effect remains to be delineated. In this study, we determined that BA treatment in HeLa cells increased the sumoylation of Sp1 by inhibiting sentrin-spec...

The role of Sp1 in controlling gene expression in lung tumor development and metastasis is not well understood. In this study, we showed that the Sp1 level was highly increased and required for lung tumor growth in transgenic mice bearing Kras-induced lung tumors under the control of doxycycline. Furthermore, the Sp1 level was highly upregulated in...

Previous study has known that Sp1 inhibited by a natural product, betulinic acid (BA), involves in the cancer progression, but the mechanism still need to delineate. In this study, we found that BA treatment increases the sumoylation of Sp1 by inhibiting the SUMO1/sentrin specific peptidase 1 (SENP1), increasing the recruitment of E3 ligase, RNF4,...

The sigma‐1 receptor (Sig‐1R) is an endoplasmic reticulum (ER)‐resident non‐opioid receptor that is expressed in the nervous system and can regulate cellular differentiation, neuroplasticity, and neuroprotection. Nuclear lamins in the nucleus are essential for the nuclear envelope assembly, DNA synthesis, and gene transcription. We tested here the...

Sp1 is important for the transcription of many genes. Our previous studies have shown that Sp1 is degraded in normal cell, but it is preserved in cancer cells during mitosis and exists a priori in the daughter cells, ready to engage in gene transcription and thereby contributes to the proliferation and survival of cancer cells. The mechanism by whi...

Most studies on heat shock protein 90 (Hsp90) have focused on the involvement of Hsp90 in the interphase, whereas the role of this protein in the nucleus during mitosis remains largely unclear. In this study, we found that the level of the acetylated form of Hsp90 decreased dramatically during mitosis, which indicates more chaperone activity during...

Sp1 is an important transcription factor for a number of genes that regulate cell growth and survival. Sp1 is an anchor protein that recruits other factors to regulate its target genes positively or negatively, but the mechanism of its functional switch by which positive or negative coregulators are recruited is not clear. In this study, we found t...