MALAT1 overexpression promotes the growth of colon cancer by repressing β-catenin degradation

Zheng, Xiaoying; Ren, Jianhua; Peng, Bingjun; Ye, Jun-Ling; Wu, Xinchun; Zhao, Wenhui; Li, Yanjun; Chen, Ruihui; Gong, Xue; Bai, Chengmei; Wang, Yating; Zhao, Hong; Zhang, Yiqing

doi:10.1016/j.cellsig.2020.109676

Cited by 14 publications

(11 citation statements)

References 18 publications

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“…These results indicated significant changes in the level of pro-inflammatory oncogenic cytokine (IL-6), antioxidant enzyme (SOD1), a pro-transcription activator of Wnt signaling cascade (β-catenin), and the dynamic tumor transcription factor (NF-κB). There was a high correlation between the overexpression of the potential prognostic factor, β-catenin, and the progression of colorectal cancer from normal epithelial tissue, polyps, and adenomas to carcinomas in colorectal cancer patients 12 13 and levels of SOD and IL-6 were closely related to cancer risk. 14 15 The results confirmed that oral intake of low doses-BaP caused harmful effects by inducing DNA adducts by increasing the inflammation (i.e., IL-6) and oxidative stress (i.e., SOD1) in the stomach and colon.…”

Section: Discussionmentioning

confidence: 97%

The Risk of Gastrointestinal Cancer on Daily Intake of Low-Dose BaP in C57BL/6 for 60 Days

Zheng

Park

Kwon³

et al. 2022

J Korean Med Sci

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Background Benzo(a)pyrene (BaP) is a carcinogenic compound in contaminated foodstuffs. The effect of oral intake of the environmental carcinogen BaP under low doses and frequent exposure on a digestive system has not been thoroughly verified. Methods In this regard, this study was conducted to prove the toxicity effects of BaP on the stomach and colon tissue after exposure to C57BL/6 mouse (3 and 6 µg/kg) following daily oral administration for 60 days. This study investigated acute gastric mucosal injury, severe gastric edema, cell infiltration, and mononuclear cells, multifocal cells, and tumoral inflammatory cells. Results The results of ELISA showed that the expression of serum interleukin (IL)-6 and tumor necrosis factor-α in the BaP exposure group were significantly increased, and a high level of DNA adduct distribution in their stomach and colon. Moreover, this study has confirmed the expression of early carcinogenesis markers: nuclear factor (NF)-κB, p53, IL-6, superoxide dismutase 1 (SOD1), mucin (MUC1 and MUC2), and β-catenin in the stomach and colon, and showed that there was a significant increase in IL-6, NF-κB, SOD1, β-catenin, and MUC1 ( P < 0.05). At the same time, there was a significant decrease in MUC2 and p53 ( P < 0.05). Thus, even in low doses, oral intake of BaP can induce DNA damage, increasing the potential risk of gastrointestinal cancer. Conclusion This study will provide a scientific basis for researching environmental contaminated food and intestinal health following daily oral administration of BaP.

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Section: Discussionmentioning

confidence: 97%

The Risk of Gastrointestinal Cancer on Daily Intake of Low-Dose BaP in C57BL/6 for 60 Days

Zheng

Park

Kwon³

et al. 2022

J Korean Med Sci

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“…In addition, Co-IP as well as protein stability and degradation assays revealed the relationship between TRIM50 and β -catenin. A published study by Zheng et al found that inhibiting β -catenin degradation can promote the development of colon cancer [ 35 ]. Moreover, suppression of the Wnt/ β -catenin pathway in GC cells by treatment with XAV939 obviously inhibited TRIM50 knockdown-induced cell proliferation, cycle progression, migration, invasion and the expression of the Wnt/ β -cateninpathway-related proteins.…”

Section: Discussionmentioning

confidence: 99%

TRIM50 Inhibits Proliferation and Metastasis of Gastric Cancer via Promoting β-Catenin Degradation

Jin

et al. 2022

Journal of Oncology

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Background. Gastric cancer (GC) is a common malignancy with a poor prognosis. Tripartite motif-containing 50 (TRIM50) belongs to the TRIM family and is reported to be related to numerous cancers. This study aimed to investigate the function of TRIM50 in GC. Methods. Three microarray datasets (GSE13911, GSE79973, and GSE19826) containing GC and adjacent nontumor tissues were used for bioinformatics analysis to screen GC-related genes and assess the associations between GC development and TRIM50 expression. Then, TRIM50 expression in GC cells was detected at mRNA and protein levels. After TRIM50 was knockdown or overexpressed, the effect of TRIM50 on the proliferation and metastasis of GC cells was analyzed using Cell Counting Kit-8 (CCK-8), flow cytometry, scratch, and Transwell assays. The interaction between TRIM50 and β-catenin was analyzed. The expression of cell cycle-, migration-, invasion-, and Wnt/β-catenin signaling pathway-related proteins was detected by Western blot. Furthermore, we measured the role of TRIM50 overexpression on tumor growth as well as the Wnt/β-catenin signaling pathway in vivo. In addition, XAV939 (a WNT/β-catenin signaling pathway inhibitor) was used to clarify the mechanism of TRIM50 on GC. Results. Bioinformatics revealed that TRIM50 expression was decreased in GC samples and associated with GC development. In vitro study revealed that TRIM50 overexpression impeded the GC cell proliferation and metastasis, while TRIM50 knockdown presented the opposite results. In addition, TRIM50 interacted with β-catenin to induce the degradation of β-catenin. In in vivo assay, TRIM50 overexpression inhibited tumor growth and blocked the Wnt/β-catenin signaling pathway. In addition, TRIM50 knockdown-promoted cell proliferation and metastasis in GC cells were inverted by XAV939. Conclusion. TRIM50 overexpression may inhibit cell proliferation and metastasis in GC via β-catenin degradation, indicating that TRIM50 could be a target for the treatment of GC.

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“…MALAT1 is overexpressed in many types of cancer (Goyal et al 2021 ), including CRCs (Younis et al 2022 ; Uthman et al 2021 ; Hu et al 2021 ; Zheng et al 2020 ; Xiong et al 2018 ; Yang et al 2015 ), metastatic lung cancers (Shen et al 2015 ), advanced stages of pancreatic cancers (Pang et al 2015 ). In general, high levels of MALAT1 expression have been demonstrated in the vast majority of CRC specimens compared to adjacent non-tumor control colorectal tissue specimens in cancer patients (Sun et al 2019b ; Zheng et al 2020 ; Luan et al 2020 ; Xiong et al 2018 ; Li et al 2017a ). Moreover, MALAT1 expression was significantly higher in advanced stages III–IV of tumor-node-metastasis (TNM) (Labianca et al 2013 ) than in early stages I–II of CRC (Luan et al 2020 ).…”

Section: Malat1 and Other Lncrnas Affecting The Level Of Ty...mentioning

confidence: 99%

MALAT1-miRNAs network regulate thymidylate synthase and affect 5FU-based chemotherapy

Matuszyk

2022

Mol Med

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Background The active metabolite of 5-Fluorouracil (5FU), used in the treatment of several types of cancer, acts by inhibiting the thymidylate synthase encoded by the TYMS gene, which catalyzes the rate-limiting step in DNA replication. The major failure of 5FU-based cancer therapy is the development of drug resistance. High levels of TYMS-encoded protein in cancerous tissues are predictive of poor response to 5FU treatment. Expression of TYMS is regulated by various mechanisms, including involving non-coding RNAs, both miRNAs and long non-coding RNAs (lncRNAs). Aim To delineate the miRNAs and lncRNAs network regulating the level of TYMS-encoded protein. Main body Several miRNAs targeting TYMS mRNA have been identified in colon cancers, the levels of which can be regulated to varying degrees by lncRNAs. Due to their regulation by the MALAT1 lncRNA, these miRNAs can be divided into three groups: (1) miR-197-3p, miR-203a-3p, miR-375-3p which are downregulated by MALAT1 as confirmed experimentally and the levels of these miRNAs are actually reduced in colon and gastric cancers; (2) miR-140-3p, miR-330-3p that could potentially interact with MALAT1, but not yet supported by experimental results; (3) miR-192-5p, miR-215-5p whose seed sequences do not recognize complementary response elements within MALAT1. Considering the putative MALAT1-miRNAs interaction network, attention is drawn to the potential positive feedback loop causing increased expression of MALAT1 in colon cancer and hepatocellular carcinoma, where YAP1 acts as a transcriptional co-factor which, by binding to the TCF4 transcription factor/ β-catenin complex, may increase the activation of the MALAT1 gene whereas the MALAT1 lncRNA can inhibit miR-375-3p which in turn targets YAP1 mRNA. Conclusion The network of non-coding RNAs may reduce the sensitivity of cancer cells to 5FU treatment by upregulating the level of thymidylate synthase.

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MALAT1 overexpression promotes the growth of colon cancer by repressing β-catenin degradation

Cited by 14 publications

References 18 publications

The Risk of Gastrointestinal Cancer on Daily Intake of Low-Dose BaP in C57BL/6 for 60 Days

The Risk of Gastrointestinal Cancer on Daily Intake of Low-Dose BaP in C57BL/6 for 60 Days

TRIM50 Inhibits Proliferation and Metastasis of Gastric Cancer via Promoting β-Catenin Degradation

MALAT1-miRNAs network regulate thymidylate synthase and affect 5FU-based chemotherapy

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