Long Noncoding RNA <i>ELIT-1</i> Acts as a Smad3 Cofactor to Facilitate TGFβ/Smad Signaling and Promote Epithelial–Mesenchymal Transition

Sakai, Satoshi; Ohhata, Tatsuya; Kitagawa, Kyoko; Uchida, Chiharu; Aoshima, Takuya; Niida, Hiroyuki; Suzuki, Tetsuro; Inoue, Yasumichi; Miyazawa, Keiji; Kitagawa, Masatoshi

doi:10.1158/0008-5472.can-18-3210

Cited by 87 publications

(65 citation statements)

References 61 publications

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“…TGF-β is a multifunctional regulatory protein that can regulate multiple cellular processes, and is known to be particularly important in tumor metastasis [ 9 , 10 ]. It promotes tumor progression by facilitating the invasion of various types of tumor cells via EMT [ 11 , 12 ]. The underlying regulatory mechanisms of TGF-β-induced EMT in NPC remain unclear.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-296-5p inhibits cell metastasis and invasion in nasopharyngeal carcinoma by reversing transforming growth factor-β-induced epithelial–mesenchymal transition

Chen

Luo

et al. 2020

Cell Mol Biol Lett

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Aim To explore the effect of miR-296-5p on the metastasis of nasopharyngeal carcinoma (NPC) cells and investigate the underlying mechanism. Methods The expressions of miR-296-5p in NPC tissues and cells were determined using GSE32920 database analysis and real-time PCR and miRNA microarray assays. An miR-296-5p mimic and inhibitor were transfected into NPC cells. Then, immunofluorescence imaging, scratch wound-healing, transwell migration and invasion assays were used to observe the effects of miR-296-5p on cell metastasis and invasion. Real-time PCR and western blotting were carried out to detect the expressions of genes and proteins related to epithelial–mesenchymal transition (EMT). A dual luciferase reporter assay was used to identify whether TGF-β is the target gene of miR-296-5p. Finally, TGF-β expression plasmids were transfected into NPC cells to verify the role of TGF-β in the miR-296-5p-mediated inhibition of nasopharyngeal carcinoma cell metastasis. Results Our results show that miR-296-5p inhibits the migratory and invasive capacities of NPC cells by targeting TGF-β, which suppresses EMT. Importantly, the miR-296-5p level was significantly lower in human NPC tissues than in adjacent normal tissues. It also negatively correlated with TGF-β and was significantly associated with the lymph node metastasis of patients with NPC. Conclusions Our findings show that miR-296-5p represses the EMT-related metastasis of NPC by targeting TGF-β. This provides new insight into the role of miR-296-5p in regulating NPC metastasis and invasiveness.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-296-5p inhibits cell metastasis and invasion in nasopharyngeal carcinoma by reversing transforming growth factor-β-induced epithelial–mesenchymal transition

Chen

Luo

et al. 2020

Cell Mol Biol Lett

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“…Accumulating evidence indicates that lncRNAs play a crucial role in human diseases, especially in various cancers. [17][18][19][20][21][22][23][24][25][26][27][28] LncRNAs participate in almost all cellular sh-TP-53, sh-ESR1, and sh-NC. D, DDX3 and YY1 coimmunoprecipitation and western blot assay were conducted in DLD-1 cells, which transfected the overexpression of TCONS_00012883 and controls.…”

Section: Discussionmentioning

confidence: 99%

“…19 LncRNA ELIT-1 facilitates TGF-β/Smad signaling through interacting with Smad3. 20 Although researches on lncRNAs have progressed rapidly, the functions of most lncRNAs are still unclear. Therefore, it is essential to explore the functions of lncRNAs in CRC progression.…”

Section: Introductionmentioning

confidence: 99%

TCONS_00012883 promotes proliferation and metastasis via DDX3/YY1/MMP1/PI3K‐AKT axis in colorectal cancer

Yang

Peng

et al. 2020

Clinical & Translational Med

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Background: Long noncoding RNAs (lncRNAs) have emerged as key regulators in multiple cancers, including colorectal cancer (CRC). However, the biological functions and molecular mechanisms underlying most lncRNAs in CRC remain largely unknown. Methods: A novel lncRNA (TCONS_00012883) was identified using RNA sequencing. The level of TCONS_00012883 expression in CRC was analyzed by qRT-PCR. The biological functions of TCONS_00012883 in CRC were investigated by a series of in vitro and in vivo experiments: CCK8, colony formation, EdU, flow cytometric assays, transwell assays, and mouse xenograft. The molecular mechanisms of TCONS_00012883 were demonstrated by RNA pulldown, mass spectrometry analysis, RIP, coimmunoprecipitation, RNA sequencing, chromatin immunoprecipitation, and rescue experiments. Results: Elevated expression of TCONS_00012883 was confirmed in CRC and positively associated with a poor prognosis. Functionally, gain-and loss-offunction assays indicated that TCONS_00012883 promoted proliferation and metastasis of CRC cell lines in vitro and in vivo. Mechanistically, RNA pulldown and mass spectrometry analysis showed that DEAD-box helicase 3 (DDX3) was the protein partner of TCONS_00012883. Furthermore, RNA sequencing assay revealed that matrix metallopeptidase 1 (MMP1) was the downstream of TCONS_00012883. Intriguingly, we found that transcription factor (YY1) could serve as a bridge between TCONS_00012883, DDX3, and MMP1. Conclusions: TCONS_00012883 significantly promoted CRC progression via the DDX3/YY1/MMP1 axis, and thus, may act as a major role in diagnosis and therapy of CRC.

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“…We also found that down-regulation of LTBP1 was accompanied by decreased expression of TGFβ, N-cadherin and vimentin, as well as increased expression of E-cadherin in ESCC cells, suggesting that LTBP1 may involve in regulating the secretion and activation of TGFβ and play an important role in promoting EMT in ESCC cells. TGFβ is the most well-known stimulator of EMT and metastasis in cancer [28,29], so we treated ESCC cells with TGFβ in our study. The results showed that LTBP1 altered the expression of proteins associated with TGFβ-induced EMT.…”

Section: Discussionmentioning

confidence: 99%

LTBP1 promotes esophageal squamous cell carcinoma progression through epithelial-mesenchymal transition and cancer-associated fibroblasts transformation

et al. 2020

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Background: Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent cancers worldwide. Due to its high morbidity and mortality rates, it is urgent to find a molecular target that contributes to esophageal carcinogenesis and progression. In this research, we aimed to investigate the functions of Latent transforming growth factor β binding protein 1(LTBP1) in ESCC progression and elucidate the underlying mechanisms. Methods: The tandem mass tag-based quantitative proteomic approach was applied to screen the differentially expressed proteins (DEPs) between 3 cases of ESCC tumor samples and paired normal tissues. Then the DEPs were validated in human ESCC tissues using western blot assays and GEPIA database respectively. The expression level of LTBP1 was detected in 152 cases of ESCC tissues and paired normal tissues. Loss-of-function assays were performed to detect the function of LTBP1 in vivo and in vitro. Immunofluorescence and Western blot assays were used to detect the expression of apoptosis, epithelial-mesenchymal transition (EMT) and cancer-associated fibroblasts (CAFs) markers. Results: A total of 39 proteins were screened to be up-regulated (ratio > 2.0) in all three ESCC tissues. The results of immunohistochemistry assays indicated that the expression level of LTBP1 was higher in ESCC tissues than that in paired normal tissues (p < 0.001). Overexpression of LTBP1 was positively associated with lymphatic metastasis in ESCC (p = 0.002). Down-regulation of LTBP1 inhibited the invasion and migration as well as metastatic abilities in vitro and in vivo. It was also observed the down-regulation of LTBP1 not only decreased the mesenchymal phenotypes but also inhibited TGFβ-induced EMT in ESCC cells. We further found that down-regulation of LTBP1 enhanced ESCC cells' sensitivity to 5-FU treatment. Inhibition of LTBP1 expression could also attenuate induction of CAFs transformation and restrain fibroblast express fibronectin (FN1) in ESCC cells.

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Long Noncoding RNA ELIT-1 Acts as a Smad3 Cofactor to Facilitate TGFβ/Smad Signaling and Promote Epithelial–Mesenchymal Transition

Abstract: Nucleus Cytoplasm TGF Smad3 P Smad4 ELIT-1 Positive feedback loop Snail, Vimentin, PAI-1 etc

Cited by 87 publications

References 61 publications

MicroRNA-296-5p inhibits cell metastasis and invasion in nasopharyngeal carcinoma by reversing transforming growth factor-β-induced epithelial–mesenchymal transition

MicroRNA-296-5p inhibits cell metastasis and invasion in nasopharyngeal carcinoma by reversing transforming growth factor-β-induced epithelial–mesenchymal transition

TCONS_00012883 promotes proliferation and metastasis via DDX3/YY1/MMP1/PI3K‐AKT axis in colorectal cancer

LTBP1 promotes esophageal squamous cell carcinoma progression through epithelial-mesenchymal transition and cancer-associated fibroblasts transformation

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