Inhibitor of DNA-Binding Protein 4 Suppresses Cancer Metastasis through the Regulation of Epithelial Mesenchymal Transition in Lung Adenocarcinoma

Wang, Chi-Chung; Hsu, Yuan-Ling; Chang, Chi-Jen; Wang, Chia-Jen; Hsiao, Tzu‐Hung; Pan, Szu-Hua

doi:10.3390/cancers11122021

Cited by 10 publications

(10 citation statements)

References 59 publications

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“…A wealth of evidence suggests that epithelial-mesenchymal transition (EMT) plays pivotal roles in migration and metastasis of tumor cells. [4][5][6] Transforming growth factor-β (TGF-β) is major inducer of EMT, which is known to be expressed in most adenocarcinomas including LUAD and associates with cancer cell metastasis. [7][8][9][10] Long noncoding RNAs (lncRNAs) are defined as transcripts of length > 200 nucleotides with a low coding potential.…”

Section: Introductionmentioning

confidence: 99%

Novel long non‐coding RNA LINC02323 promotes epithelial‐mesenchymal transition and metastasis via sponging miR‐1343‐3p in lung adenocarcinoma

Zhang

Han

et al. 2020

Thoracic Cancer

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Background We have previously developed a unique metastasis‐associated signature consisting of six long non‐coding RNAs (lncRNAs), including a novel lncRNA, namely LINC02323. In the present study, we aimed to investigate the underlying roles of LINC02323 in the migration, invasion and TGF‐β‐induced epithelial‐mesenchymal transition (EMT) of lung adenocarcinoma (LUAD) cells. Methods The distribution of LINC02323 was detected by the nuclear‐plasma separation experiment. Cell proliferation was assessd by MTT assay, and cell migration and invation were detected by transwell assays. EMT was detected by RT‐qPCR and western blotting. Interaction between miRNA and LINC02323 was predicted by starBase v2.0 and confirmed by the double luciferase reporting system. Results LINC02323 was distributed in the cytoplasm and nucleus. The overexpression or deletion of LINC02323 did not affect the proliferation of LUAD cells, while significantly affected the migration and invasion of LUAD cells. TGF‐β‐induced EMT process was significantly affected by both RNA interference (RNAi) and overexpression of LINC02323. The predicted results showed that there were binding sites between LINC02323 and miR‐1343‐3p. The expression of LINC02323 was found to be negatively correlated with miR‐1343‐3p in LUAD by analyzing The Cancer Genome Atlas (TCGA) database. The double luciferase reporting system, RT‐qPCR and western blotting experiments confirmed that LINC02323 could bind to miR‐1343‐3p, which bound to TGF‐β receptor 1 (TGFBR1). Inhibition of miR‐1343‐3p reversed LINC02323 silencing‐mediated suppression of migration, invasion and EMT. Conclusions LINC02323 acts as a competing endogenous RNA (ceRNA), which sponged miR‐1343‐3p to upregulate the TGFBR1 expression and promote the EMT and metastasis in LUAD. Key points Significant findings of the study LINC02323 promotes epithelial‐mesenchymal transition and metastasis via sponging miR‐1343‐3p in lung adenocarcinoma. What this study adds LINC02323 is a key molecule in the process of invasion and metastasis of LUAD and might be used as a potential target in metastatic cancer.

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Section: Introductionmentioning

confidence: 99%

Novel long non‐coding RNA LINC02323 promotes epithelial‐mesenchymal transition and metastasis via sponging miR‐1343‐3p in lung adenocarcinoma

Zhang

Han

et al. 2020

Thoracic Cancer

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“…Furthermore, 2 h coriloxin treatment also reduced the CL1-5 cells’ p-AKT levels. Aware that the epithelial–mesenchymal transition (EMT) contributes critically to cancer cell metastasis [ 19 ], we examined the levels of EMT-related markers in the cells. Coriloxin dose-dependently lowered the levels of vimentin and N-cad, which are mesenchymal markers ( Figure 5 B).…”

Section: Resultsmentioning

confidence: 99%

Coriloxin Exerts Antitumor Effects in Human Lung Adenocarcinoma Cells

Kuo

Wang

Peng

et al. 2022

IJMS

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Both in Taiwan and around the world, lung cancer is a primary cause of cancer-related deaths. In Taiwan, the most prevalent form of lung cancer is lung adenocarcinoma, a type of non-small-cell lung carcinoma. Although numerous lung cancer therapies are available, their clinical outcomes are unsatisfactory. Natural products, including fungal metabolites, are excellent sources of pharmaceutical compounds used in cancer treatment. We employed in vitro cell invasion, cell proliferation, cell migration, cell viability, and colony formation assays with the aim of evaluating the effects of coriloxin, isolated from fermented broths of Nectria balsamea YMJ94052402, on human lung adenocarcinoma CL1-5 and/or A549 cells. The potential targets regulated by coriloxin were examined through Western blot analysis. The cytotoxic effect of coriloxin was more efficiently exerted on lung adenocarcinoma cells than on bronchial epithelial cells. Moreover, low-concentration coriloxin significantly suppressed adenocarcinoma cells’ proliferative, migratory, and clonogenic abilities. These inhibitory effects were achieved through ERK/AKT inactivation, epithelial–mesenchymal transition regulation, and HLJ1 expression. Our findings suggest that coriloxin can be used as a multitarget anticancer agent. Further investigations of the application of coriloxin as an adjuvant therapy in lung cancer treatment are warranted.

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“…Id1 opposed twist activity, thus promoting cell metastasis to the lung via EMT [23]. It has been indicated that Id4 can inhibit lung cancer metastasis and mesenchymal-epithelial transition (MET) by binding to slug and promoting E-cadherin expression [24]. MMPs are also important markers of EMT and play a major role in the biological behaviours of cells such as cell proliferation, migration, and differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…Id proteins dimerize with bHLH protein, which inhibits their DNA binding activity [28]. In the lung cancer, Id4 binds to slug, which interferes with its interaction with E-box promoter, and then suppresses the metastasis of cancer cells [24]. Id4 interacts with MDC1 and other DNA repair proteins which govern the DNA damage response [29].…”

Section: Discussionmentioning

confidence: 99%

Id4 Suppresses the Growth and Invasion of Colorectal Cancer HCT116 Cells through CK18-Related Inhibition of AKT and EMT Signaling

Chen

Sun

et al. 2021

Journal of Oncology

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Id4 is one of the inhibitors of DNA-binding proteins (Id) and involved in the pathogenesis of numerous cancers. The specific mechanism underlying the Id4-mediated regulation of proliferation, invasion, and metastasis of colorectal cancer (CRC) cells is still largely unclear. In the present study, results showed CRC cells had a lower baseline Id4 expression than normal intestinal epithelial NCM460 cells. In order to explore the role of Id4 in the tumorigenicity, CRC HCT116 cells with stable Id4 expression were used, and results showed Id4 overexpression arrested the cell cycle at the G0/G1 phase, inhibited the cell proliferation and the colony formation, as well as suppressed the migration and invasion. In the in vivo model, Id4 overexpression inhibited the tumor growth and metastasis in the nude mice. Furthermore, Id4 overexpression upregulated the expression of proteins associated with cell proliferation, inhibited the PI3K/AKT pathway, and suppressed epithelial-mesenchymal transition (EMT) of HCT116 cells. Moreover, Id4 significantly decreased cytokeratin 18 (CK18) expression, but CK18 overexpression in Id4 expressing HCT116-Id4 cells rescued the activation of AKT, p-AKT, MMP2, MMP7, and E-cadherin. Collectively, our study indicated Id4 may inhibit CRC growth and metastasis through inhibiting the PI3K/AKT pathway in a CK18-dependent manner and suppressing EMT. Id4 may become a target for the treatment of CRC.

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Inhibitor of DNA-Binding Protein 4 Suppresses Cancer Metastasis through the Regulation of Epithelial Mesenchymal Transition in Lung Adenocarcinoma

Cited by 10 publications

References 59 publications

Novel long non‐coding RNA LINC02323 promotes epithelial‐mesenchymal transition and metastasis via sponging miR‐1343‐3p in lung adenocarcinoma

Novel long non‐coding RNA LINC02323 promotes epithelial‐mesenchymal transition and metastasis via sponging miR‐1343‐3p in lung adenocarcinoma

Coriloxin Exerts Antitumor Effects in Human Lung Adenocarcinoma Cells

Id4 Suppresses the Growth and Invasion of Colorectal Cancer HCT116 Cells through CK18-Related Inhibition of AKT and EMT Signaling

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