MiR-424 Promotes Non-Small Cell Lung Cancer Progression and Metastasis through Regulating the Tumor Suppressor Gene TNFAIP1

Zhang, Ming; Gao, Change; Yang, Yi; Li, Gaofeng; Dong, Jian; Ai, Yiqin; Ma, Qianli; Li, Wenhui

doi:10.1159/000477314

Cited by 36 publications

(25 citation statements)

References 32 publications

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“…38 Nevertheless, there were controversies regarding the expressional profile of miR-424 within tumors. To be specific, highly expressed miR-424 was detectable within squamous cell carcinoma, non-small cell lung cancer and pancreatic cancer, 20,39,40 yet no significant variation of miR-424 expression was observed within bladder epithelial carcinoma. 41 These discordances might be explained by that miR-424 functioned distinctly within various tissues and organs, which entailed further proofs.…”

Section: Discussionmentioning

confidence: 98%

“…14 Virtually, the lowly expressed miR-424 was discoverable in a broad array of other neoplasms, including glioma, cervical cancer, endometrial cancer, ovarian cancer, prostate cancer and lung cancer. [15][16][17][18][19][20] Viewed mechanically, miR-424 was capable of interfering with the expression of genes (i.e., Chk1) that were pivotal to the G1-S phase transition of cell cycle and infiltration of tumor cells (i.e., SiHa and CaSki cell lines). 16,21 Interestingly, targeting Chk1 could sensitize glioma cells against temozolomide, 22 which thereby insinuated a regulatory part of miR-424 in chemoresistance of glioma cells.…”

Section: Introductionmentioning

confidence: 99%

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<p>lncRNA CCAT2 Enhanced Resistance of Glioma Cells Against Chemodrugs by Disturbing the Normal Function of miR-424</p>

Ding¹,

Zhang²,

Chen³

et al. 2020

OTT

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These authors contributed equally to this workBackground: Aggressive metastasis of tumor cells assumed a constructive role in strengthening chemoresistance of tumors, so this investigation was intended to elucidate if lncRNA CCAT2 sponging downstream miR-424 regulated chemotolerance of glioma cells by boosting metastasis of glioma cells. Methods: One hundred and twenty-eight pairs of glioma tissues and corresponding adjacent tissues were resected from glioma patients during their operation, and we also purchased a series of glioma cell lines, including U251, U87, A172 and SHG44. Furthermore, pcDNA3.1-CCAT2, si-CCAT2, miR-424 mimic and miR-424 inhibitor were transfected into SHG44 and U251 cell lines, so as to evaluate impacts of CCAT2 and miR-424 on chemosensitivity of the glioma cells. Besides, proliferation, invasion and metastasis of the cells were determined through the implementation of colony formation assay, transwell assay and scratch assay. Results: Glioma tissues and cells were monitored with higher CCAT2 expression and lower miR-424 expression than adjacent normal tissues and NHA cell line (P<0.05). Among the glioma cell lines, the SHG44 cell line showed the strongest resistance against teniposide, temozolomide and cisplatin (P<0.05), whereas the U251 cell line was more sensitive to teniposide, temozolomide, vincristine and cisplatin than any other cell line (P<0.05). Besides, pcDNA3.1-CCAT2 and miR-424 inhibitor could enhance tolerance of glioma cell lines against drugs (P<0.05). Moreover, in-vitro transfection of si-CCAT2 and miR-424 mimic could significantly retard proliferation, invasion and migration of SHG44 and U251 cells (P<0.05), and CCAT2 was found to negatively regulate miR-424 expression by sponging it (P<0.05). In addition, CHK1 was deemed as the molecule targeted by upstream miR-424, and its overexpression can changeover the effects of miR-424 mimic on proliferation and metastasis of SHG44 and U251 cells. Conclusion: lncRNA CCAT2/miR-424/Chk1 axis might serve as a promising target for improving chemotherapeutic efficacies in glioma treatment.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

<p>lncRNA CCAT2 Enhanced Resistance of Glioma Cells Against Chemodrugs by Disturbing the Normal Function of miR-424</p>

Ding¹,

Zhang²,

Chen³

et al. 2020

OTT

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“…Further, all results highlight that CCAT1 knockdown inhibited cell proliferation by modulating cell cycle progression and cell cycle-related proteins. Cell migration and invasion are also critical factors in tumor metastasis [27]. Zhang et al demonstrated that high CCAT1 expression closely correlates with TNM stage, differentiation grade and lymph node metastasis in breast cancer patients [28], and Zhu et al reported that CCAT1 is a potential biomarker for predicting prognosis in patients with hepatocellular carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of long noncoding RNA CCAT1 inhibits cell growth, invasion and peritoneal metastasis via downregulation of Bmi-1 in gastric cancer

Jiang

Fang

et al. 2018

neo

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Long noncoding RNA colon cancer-associated transcript 1 (lncRNA CCAT1) is highly expressed in gastric cancer (GC) tissues compared with normal counterparts and CCAT1 upregulation can promote proliferation and migration of GC cells in vitro. B-cell specific moloney leukemia virus insertion site 1 (Bmi-1) expression is positively correlated with tumor progression. The present study aimed to investigate the biological functions of CCAT1 and the relationships between CCAT1 and Bmi-1 in GC progression. In the present study, CCAT1 was knocked down by specific shRNA transfection in two human GC cell lines (MGC-803 and SGC-7901). The effects of CCAT1 knockdown on GC cell proliferation, cell cycle, migration and invasion were investigated in vitro. The effect of CCAT1 knockdown on peritoneal metastasis was assessed in nude mice. Bmi-1 expression levels were examined both in vitro and in vivo. The results showed that CCAT1 knockdown markedly inhibited cell proliferation, migration and invasion, arrested the cell cycle at G0/G1 phase in vitro, and inhibited peritoneal metastasis in nude mice, along with the downregulation of Bmi-1. Taken together, CCAT1 is functionally involved in growth and metastasis of GC cells and it may be a potential target for GC therapy.

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“…In gastric cancer, overexpression of TNFAIP1 induced by knockdown of miR-372 promoted cell apoptosis via regulation of the NF-kB signaling pathway. In HeLa cell lines, overexpressed TNFAIP1 also increased cell apoptosis via downregulation of NF-kB expression [33][34][35][36]. Thus, we selected TNFAIP1 as the final target of EHMT2-induced apoptosis.…”

Section: Epigenetic Regulation Of Tnfaip1 By Ehmt2 Induced the Apoptomentioning

confidence: 99%

Histone methyltransferase EHMT2 degradation by propionate derived from Bacteroides thetaiotaomicron induced colon cancer apoptosis via epigenetic regulation of TNFAIP1

Ryu¹,

Kim²,

Han³

et al. 2020

Preprint

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BackgroundBacteroides thetaiotaomicron (BT) is the second most commonly isolated bacterium in the human microbiome after B. fragilis and is involved in the hydrolysis of glycosidic bonds in dietary carbohydrates. Although the human microbiome has recently been shown to affect colorectal cancer (CRC) treatment, the mode of action (MOA) between the microbiome and CRC is still unclear. MethodsTo assess the colon cancer apoptosis, we performed western blot, qRT-PCR and FACS analysis using BT supernatant (Sup), sodium propionate (SP), and EHMT2 specific siRNA. Using RNA-seq analysis and ChIP-seq analysis, we identified HECTD2 (E3 ligase) and TNFAIP1 (EHMT2 target) genes. The antitumor activity of EHMT2 was determined by an in vivo xenograft model. ResultsWe selected propionate derived from BT and showed that it suppressed CRC growth by promoting proteasomal degradation of EHMT2 through HECTD2 upregulation. Moreover, downregulation of EHMT2 reduced the level of H3K9me2 on the promoter region of TNFAIP1, and subsequently, upregulation of TNFAIP1 induced apoptosis of CRC cells. Finally, we performed an in vivo study using BIX01294 to inactivate EHMT2 and observed a reduction in the tumor size of the CRC xenograft models. ConclusionsWe suggest anticancer effects of BT and EHMT2 as therapeutic targets for colon cancer treatment, and we will provide the possibility for synergistic effects of an EHMT2 inhibitor and BT in CRC treatment. *Authors share co-first authorshipBackground Colorectal cancer (CRC) is a major cancer worldwide. Although chemotherapy (5-fluorouracil (5-FU) and oxaliplatin) and targeted therapy (cetuximab and bevacizumab) are used to treat this disease, new therapeutic methods are needed to reduce the side effects and increase the success rate of CRC 4 treatment [1][2][3]. Recently, the human microbiome, including metabolites and microbiota, has been studied to identify alternative new CRC treatments [4][5][6].In the human body, the microbiota mainly colonizes the large intestine and promotes food digestion, regulation of the human immune system, production of vitamins (B12, K, riboflavin), and protection against disease-related bacteria [7][8][9]. In the colon, the Bacteroides genus is a major group of the human microbiome, and Bacteroides thetaiotaomicron (BT) is the second most commonly isolated bacteria after B. fragilis [10][11][12]. BT is a gram-negative obligate anaerobe. This bacterium is involved in polysaccharide metabolism, such as hydrolysis of glycosidic bonds in dietary carbohydrates [10]. In colon cancer, the major bacterium B. fragilis showed suppression of inflammation-associated CRC development via polysaccharide A production [13]. In other words, B. fragilis-derived toxins induced CRC development [14]. Although BT is the second most commonly isolated bacterium in the human microbiome, the relationship between BT and CRC is still unclear. Thus, we examined the anticancer effects of BT using CRC cell lines and elucidated the molecular mechanism of BT-induced apoptosis of CRC cells via epig...

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MiR-424 Promotes Non-Small Cell Lung Cancer Progression and Metastasis through Regulating the Tumor Suppressor Gene TNFAIP1

Cited by 36 publications

References 32 publications

<p>lncRNA CCAT2 Enhanced Resistance of Glioma Cells Against Chemodrugs by Disturbing the Normal Function of miR-424</p>

<p>lncRNA CCAT2 Enhanced Resistance of Glioma Cells Against Chemodrugs by Disturbing the Normal Function of miR-424</p>

Knockdown of long noncoding RNA CCAT1 inhibits cell growth, invasion and peritoneal metastasis via downregulation of Bmi-1 in gastric cancer

Histone methyltransferase EHMT2 degradation by propionate derived from Bacteroides thetaiotaomicron induced colon cancer apoptosis via epigenetic regulation of TNFAIP1

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