LAMB3 promotes tumour progression through the AKT–FOXO3/4 axis and is transcriptionally regulated by the BRD2/acetylated ELK4 complex in colorectal cancer

Zhu, Zhehui; Song, Jinglue; Guo, Yao; Huang, Zhenyu; Chen, Xiaojian; Dang, Xuening; Huang, Yuji; Wang, Yuhan; Ou, Weijun; Yang, Yili; Yu, Wei; Liu, Chenying; Cui, Long

doi:10.1038/s41388-020-1321-5

Cited by 65 publications

(64 citation statements)

References 42 publications

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“…On the other hand, the down-regulated genes (other than TXNIP) may also play a role in mediating the growth-suppressive effect of anisomycin. It has been reported that LAMB3 overexpression is a marker of poor prognosis in colorectal cancer, and that LAMB3 promotes migration in vitro and tumor growth and metastasis in vivo [ 24 ]. Down regulation of LAMB3 and LAMA3, which are components of Laminin-332 protein [ 25 ], may contribute to the effects of anisomycin.…”

Section: Discussionmentioning

confidence: 99%

Analysis of differentially expressed genes responsible for the suppressive effect of anisomycin on cell proliferation of DLD-1 cells

Ushijima

Monzaki

Funakoshi

2021

Biochemistry and Biophysics Reports

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Anisomycin is used as a chemical compound that possesses c-Jun N-terminal kinase (JNK)-activating effects. Recently, the potent anti-tumor effects of anisomycin have received much attention. In addition to its JNK-activating effects, anisomycin has been reported to affect gene expression in osteosarcoma, leukemia, hepatocellular carcinoma, ovarian cancer and other cancers. We previously demonstrated that anisomycin induced the degradation of transcription factor GATA-6 in DLD-1 cells (a colorectal cancer cell line) and inhibited their proliferation. However, the details of the gene network involved in the process remain unclear. In this study, we conducted an RNA-seq analysis of differentially expressed genes (DEGs) in anisomycin-treated DLD-1 cells to identify the molecular process of growth-suppressive genes. We found that LAMB3, which regulates cell adhesion and migration, and NFKB2 were down-regulated by anisomycin. In addition, the mRNA expression of several tumor suppressor genes (ATF3, ERRFI1, KLF6, and AKAP12) was transiently enhanced at 3 h after anisomycin treatment. These results suggest that anisomycin blocks a PI3K/Akt-signaling cascade to lead to the suppression of cell growth.

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Section: Discussionmentioning

confidence: 99%

Analysis of differentially expressed genes responsible for the suppressive effect of anisomycin on cell proliferation of DLD-1 cells

Ushijima

Monzaki

Funakoshi

2021

Biochemistry and Biophysics Reports

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“…ELK4 (SRF accessory factor-1, SAP-1) belongs to the TCF subfamily of the ETS domain transcription factors, and was described to have crucial roles in a lot of cancers 31 . ELK4 together with SRF is a signi cant regulator for many genes, for example c-fos and LAMB3 32,33 . In the present study, we found that ELK4 overexpression promotes proliferation and invasion of GC cells.…”

Section: Disscussionmentioning

confidence: 99%

ELK4-mediated lncRNA SNHG22 promotes gastric cancer progression through interacting with EZH2 and regulating miR-200c-3p/Notch1 axis

Mao

Tao

Liu

et al. 2021

Preprint

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Background Long non-coding RNAs (lncRNAs) play important regulatory roles in the initiation and progression of various cancers. However, the biological roles and the potential mechanisms of lncRNAs in gastric cancers remain unclear. Methods The expression of SNHG22 in gastric cancer was analyzed in public databases (TCGA) and validated via qRT-PCR. SNHG22 knockdown cell lines were construced, and cell proliferation and invasion were analyzed. CHIP and luciferase reporter assays were performed to clarify the transcriptional role of ELK4. RNA pull-down followed MS and RIP assays were employed to identify the interaction between SNHG22 and EZH2. Luciferase reporter assays and RIP assays were used to confirm the regulation of SNHG22 on Notch1 by sponging miR-2003-3p. Results Knockdown of SNHG22 inhibited the proliferation and invasion ability of GC cells. Moreover, we identified that the transcriptional factor, ELK4, could promote SNHG22 expression in GC cells. In addition, using RNA pull-down followed MS assay, we found that SNHG22 directly bound to EZH2 to suppress the expression of tumor suppressor genes. At the same time, SNHG22 sponged miR-200c-3p to increase Notch1 expression. Conclusions Taken together, our findings demonstrated the role of SNHG22 on promoting proliferation and invasion of GC cells. And we revealed a new regulatory mechanism of SNHG22 in GC cells. SNHG22 is a promising lncRNA biomarker for diagnosis and prognosis and a potential target for GC treatment.

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“…CBP30, a small‐molecule inhibitor of EP300, which is the vital constituent of the CBP/p300 complex, markedly inhibits the expression of ETV4 in HCC cells ( 71 ). A-485, an inhibitor of CBP/p300, could decrease the level of acetylated ELK4 and limit its transcriptional activity ( 72 ). Besides, acetylated ETS factors could be recognized by BET proteins.…”

Section: The Therapeutic Promise In Targeting E-twenty-six Factors Inmentioning

confidence: 99%

“…BET inhibitors, some of which have been in clinical trials, could suppress the transcriptional activity and expression of ETS factors ( 74 , 75 ). For instance, transcriptional activation of ELK4 target genes could be inhibited by JQ1, a BET inhibitor, via disrupting the interaction between ELK4 and BRD2 in colorectal cancer ( 72 ). JQ1 could inhibit the function of acetylated ERG, which recruits BRD4 to promote transcriptional activation ( 76 ).…”

Section: The Therapeutic Promise In Targeting E-twenty-six Factors Inmentioning

confidence: 99%

“…MEK and KIT inhibitors impede gastrointestinal stromal tumor (GIST) growth by interrupting the KIT–ETV1-positive feedback circuit in GIST ( 78 ). Moreover, MEK inhibitor U0126 exhibits a synergetic effect with BET inhibitor JQ1 via ELK4 activity inhibition in colorectal cancer ( 72 ). Besides, the combination of MEK inhibitor PD901 and JQ1 has a more significant inhibition on the expression of several ETS factors (ELK3, ETV1, ETV4, ETV5) than MEK inhibitor alone in lung cancer ( 79 ).…”

Section: The Therapeutic Promise In Targeting E-twenty-six Factors Inmentioning

confidence: 99%

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The E-Twenty-Six Family in Hepatocellular Carcinoma: Moving into the Spotlight

et al. 2021

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Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality worldwide. Although therapeutic strategies have recently advanced, tumor metastasis and drug resistance continue to pose challenges in the treatment of HCC. Therefore, new molecular targets are needed to develop novel therapeutic strategies for this cancer. E-twenty-six (ETS) transcription family has been implicated in human malignancies pathogenesis and progression, including leukemia, Ewing sarcoma, gastrointestinal stromal tumors. Recently, increasing studies have expanded its great potential as functional players in other cancers, including HCC. This review focuses primarily on the key functions and molecular mechanisms of ETS factors in HCC. Elucidating these molecular details may provide novel potential therapeutic strategies for cancers.

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LAMB3 promotes tumour progression through the AKT–FOXO3/4 axis and is transcriptionally regulated by the BRD2/acetylated ELK4 complex in colorectal cancer

Cited by 65 publications

References 42 publications

Analysis of differentially expressed genes responsible for the suppressive effect of anisomycin on cell proliferation of DLD-1 cells

Analysis of differentially expressed genes responsible for the suppressive effect of anisomycin on cell proliferation of DLD-1 cells

ELK4-mediated lncRNA SNHG22 promotes gastric cancer progression through interacting with EZH2 and regulating miR-200c-3p/Notch1 axis

The E-Twenty-Six Family in Hepatocellular Carcinoma: Moving into the Spotlight

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