Prognostic value of LAMP3 and TP53 overexpression in benign and malignant gastrointestinal tissues

Sun, Rongwei; Wang, Xudong; Zhu, Huijun; Mei, Haijun; Wang, Wei; Zhang, Shu; Huang, Jianfei

doi:10.18632/oncotarget.2643

Cited by 69 publications

(65 citation statements)

References 36 publications

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“…Cells were further divided according to Nampt expression into "low" (Nampt low) and "high" (Nampt high) groups, according to a cutoff point. The cutoff point for Nampt expression was calculated using the X-tile software program as previously described [50]. …”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

Nicotinamide Phosphoribosyltransferase Inhibitor APO866 Prevents IL-1β-Induced Human Nucleus Pulposus Cell Degeneration via Autophagy

Shi

et al. 2018

Cell Physiol Biochem

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Background/Aims: Intervertebral discs consist of an extracellular matrix (ECM) with a central gelatinous nucleus pulposus (NP) enclosed in an outer layer known as the annulus fibrosus. ECM metabolic disorders result in loss of boundary between the annulus fibrosus and NP, which can lead to intervertebral disc degeneration (IDD). Proinflammatory cytokines, such as interleukin (IL)-1β, mediate the progression of IDD. Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the first step in the biosynthesis of nicotinamide adenine dinucleotide (NAD) and is known to be induced by IL-1β. APO866 is an inhibitor of NAD biosynthesis and is involved in autophagy. LC3 (microtubule-associated protein 1 light chain 3) is a key regulator of autophagy and is used as an indicator of increased autophagy. Herein, we investigate the role of APO866 in regulating autophagy in NP cells and IL-1β mediated NP cell degeneration and apoptosis. Methods: NP cells were extracted from IDD tissues and cultured in DMEM/F12 medium. Nampt was induced by different concentrations of IL-1β (0, 0.5, 1, 5, 10 ng/mL) for 24 h or NP cells were treated with 10 ng/mL IL-1β for 0, 6, 12, 48 h. QRT-PCR and western blots were used to detect Nampt and ECM-related protein expression in NP tissue of patients with IDD and in NP cells. Confocal analysis was used to detect membrane-bound LC3, Aggrecan, and Collagen II. Results: Nampt is expressed in NP tissue at higher levels in severe grades of IDD (Grade IV and V) compared with low grades (Grade II and III). In NP cells, 10 ng/mL IL-1β induced Nampt expression for 48 h, increased expression of the degradative-associated proteins, ADAMTS4/5 and MMP-3/13, and decreased expression of ECM-related proteins, Aggrecan and Collagen II. However, the Nampt inhibitor APO866 blocked IL-1β induction, and the knockdown of Nampt expression increased the expression of ECM proteins that were inhibited by IL-1β. Moreover, evidence provided by the autophagic markers LC3 and Beclin-1 indicated that APO866 induced NP cell autophagy. Furthermore, although APO866 inhibited the downregulated expression of ECM-related proteins by IL-1β, this function was blocked by autophagy inhibitor, 3-methyladenine. Conclusion: APO866 protects NP cells and induces autophagy by inhibiting IL-1β-induced NP cell degeneration and apoptosis, which may have therapeutic potential in IDD.

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Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

Nicotinamide Phosphoribosyltransferase Inhibitor APO866 Prevents IL-1β-Induced Human Nucleus Pulposus Cell Degeneration via Autophagy

Shi

et al. 2018

Cell Physiol Biochem

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“…It is often connected with poor differentiation of highly advanced cancer [25]. In addition, LAMP3 is overexpressed in many types of cancers [7] [9]. As demonstrated by previous studies, autophagy has a crucial role in tumor development and metastasis, mainly to lymph nodes.…”

Section: Discussionmentioning

confidence: 99%

“…This would allow to select the right treatment strategy before any adverse changes occur, including the drug resistance. In order to introduce innovative therapies, it is also necessary to find new prognostic markers and to better understand the mechanism of tumor formation [7].…”

Section: Discussionmentioning

confidence: 99%

“…High level of LAMP3 mRNA significantly correlates with poor prognosis in patients with stage I and II tumors [4] [5] [6]. Furthermore, LAMP3 takes part in the invasion and migration of cancer cells as well as the induction of autophagocytosis [7]. It also inhibits the activity of the tumor protein p53 (TP53) gene, involved in tumor metastasis and resistance to treatment.…”

Section: Introductionmentioning

confidence: 99%

“…It may affect the effectiveness of radiotherapy, chemotherapy and lead to treatment resistance. In addition, it has been shown that less oxygenated tumors have a worse prognosis and higher incidence of metastasis compared with more oxygenated tumors [1] [7]. LAMP3 is involved in unfolded protein response (UPR) signaling pathway induced by hypoxia or stress factors [6].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Transcriptional Activity of LAMP3 Gene Involved in Autophagocytosis in Colorectal Cancer LAMP3 Expression in Colorectal Cancer

Bednarczyk¹,

Muc-Wierzgoń²,

Zmarzły³

et al. 2017

JBM

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Background: Autophagocytosis is a biological process involving the controlled distribution of cell fragments and organelles in order to obtain an additional source of energy. LAMP3 (lysosome-associated membrane protein 3) is a heavily glycosylated integral membrane protein located mainly in the lysosomal membrane. Recent studies have shown that it participates in tumor metastasis and drug resistance. Its main role is contribution to tumor cells proliferation, migration and invasion. The aim of this study was to determine changes in transcriptional activity of LAMP3 at various stages of colorectal cancer. In addition, an attempt was made to select miRNAs potentially regulating LAMP3 expression using bioinformatic databases. Methods: The study was conducted on healthy colon samples and colon cancer samples in four stages. Molecular analysis included the extraction of total RNA, purification of the obtained extracts, expression profile analysis using oligonucleotide microarray technique and in silico determination of miRNAs potentially regulating the LAMP3 expression. Results: The level of LAMP3 expression is higher in colorectal adenocarcinoma cells than in non-cancerous cells and depends on the stage of the disease. Conclusions: LAMP3 may promote cancer progression, metastasis and cause the resistance to treatment.

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Correlation between Trop2 and amphiregulin coexpression and overall survival in gastric cancer

et al. 2017

Self Cite

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Gastric cancer (GC) is a multistep and multistage disease and the majority of GC cells could overexpressed one or more oncogenes. Trop2 and amphiregulin (AREG) are both overexpressed in various epithelial cell cancers and have the role in the increases tumor cells division and metastasis. However, little is known about the function and correlation of two oncogenes coexpressed in GC. The expression level of these two genes in 791 cases of GC tissues were tested, the correlations between two genes expression and clinical pathological characteristics and overall survival in GC patients through immunohistochemistry (IHC) were analyzed. This study also explored the mRNA expression level of two genes in 26 cases of freshly GC tissues by qRT‐PCR. The results indicated that Trop2+/AREG+ coexpression was higher in GC tissues than in adjacent tissues. Trop2+/AREG+ protein coexpression were associated with Tumor Node Metastasis (TNM) stage (χ 2 = 50.345, P < 0.001), tumor size (χ 2 = 40.349, P < 0.001), lymph node metastases (χ 2 = 26.481, P < 0.001), and distant metastases (χ 2 = 8.387, P = 0.039). GC patients with Trop2+ and AREG+ protein coexpression had poor overall survival rates (HR = 3.682, 95% CI = 2.038–6.654, P < 0.001). The expression level of Trop2/AREG were positively correlated (r 0.254 and P < 0.001). The result of the mRNA expression was similar to that of the protein expression. Overall, Trop2 and AREG could be seen as prognostic cobiomarker in GC and combined detection of Trop2 and AREG could be viewed as helpful in predicting the prognosis of the GC patients.

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Prognostic value of LAMP3 and TP53 overexpression in benign and malignant gastrointestinal tissues

Cited by 69 publications

References 36 publications

Nicotinamide Phosphoribosyltransferase Inhibitor APO866 Prevents IL-1β-Induced Human Nucleus Pulposus Cell Degeneration via Autophagy

Nicotinamide Phosphoribosyltransferase Inhibitor APO866 Prevents IL-1β-Induced Human Nucleus Pulposus Cell Degeneration via Autophagy

The Transcriptional Activity of LAMP3 Gene Involved in Autophagocytosis in Colorectal Cancer LAMP3 Expression in Colorectal Cancer

Correlation between Trop2 and amphiregulin coexpression and overall survival in gastric cancer

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