Long Non-Coding RNA MNX1-AS1 Promotes Progression of Triple Negative Breast Cancer by Enhancing Phosphorylation of Stat3

Li, Junhua; Li, Qingjian; Li, Danhua; Shen, Zhiwen; Zhang, Kun; Bi, Zhuofei; Li, Yujuan

doi:10.3389/fonc.2020.01108

Cited by 22 publications

(16 citation statements)

References 22 publications

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“…et al. found that the MNX1-AS1 lncRNA was able to enhance STAT3 phosphorylation, thereby driving TNBC progression ( 24 ). ADAMTS9-AS2 has also previously been shown to suppress lung and ovarian cancer growth ( 17 , 19 ), but its functional role in TNBC has not been previously clarified.…”

Section: Discussionmentioning

confidence: 99%

The lncRNA ADAMTS9-AS2 Regulates RPL22 to Modulate TNBC Progression via Controlling the TGF-β Signaling Pathway

Huang²,

Zhu³

et al. 2021

Front. Oncol.

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BackgroundLong non-coding RNAs (lncRNAs) are key regulators of triple-negative breast cancer (TNBC) progression, but further work is needed to fully understand the functional relevance of these non-coding RNAs in this cancer type. Herein, we explored the functional role of the lncRNA ADAMTS9-AS2 in TNBC.MethodsNext-generation sequencing was conducted to compare the expression of different lncRNAs in TNBC tumor and paracancerous tissues, after which ADAMTS9-AS2differential expression in these tumor tissues was evaluated via qPCR. The functional role of this lncRNA was assessed by overexpressing it in vitro and in vivo. FISH and PCR were used to assess the localization of ADAMTS9-AS2within cells. Downstream targets of ADAMTS9-AS2 signaling were identified via RNA pulldown assays and transcriptomic sequencing.ResultsThe expression ofADAMTS9-AS2 was decreased in TNBC tumor samples (P < 0.05), with such downregulation being correlated with TNM stage, age, and tumor size. Overexpressing ADAMTS9-AS2 promoted the apoptotic death and cell cycle arrest of tumor cells in vitro and inhibited tumor growth in vivo. From a mechanistic perspective, ADAMTS9-AS2 was found to control the expression of RPL22 and to thereby modulate TGF-β signaling to control TNBC progression.ConclusionADAMTS9-AS2 controls the expression of RPL22 and thereby regulates TNBC malignancy via the TGF-β signaling pathway.

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Section: Discussionmentioning

confidence: 99%

The lncRNA ADAMTS9-AS2 Regulates RPL22 to Modulate TNBC Progression via Controlling the TGF-β Signaling Pathway

Huang²,

Zhu³

et al. 2021

Front. Oncol.

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“…In this step, we deleted four articles since they provided unavailable data [ 40 ] or data from TCGA or CEO [ 12 , 26 , 27 ]. Finally, 10 articles were chosen for this meta-analysis [ 12 , 15 , 17–19 , 22 , 23 , 27–29 ]. The flow diagram of study search and selection is summarized in Figure 1 .…”

Section: Resultsmentioning

confidence: 99%

“…In breast cancer, Cheng et al [ 16 ] first proposed MNX1-AS1 acted as a functional oncogene that could induce the epithelial-mesenchymal transition of cancer cells via activation of AKT/mTOR signaling pathway and upregulation of its natural sense transcript MNX1. Besides, a most recent study revealed MNX1-AS1 could enhance the aggressiveness of triple-negative breast cancer cells through interacting with Stat3 and increasing its phosphorylation in a p-JAK-dependent manner [ 17 ]. In prostate cancer, MNX1-AS1 was proved to facilitate cancer cell proliferation, migration, and invasion, but its molecular mechanisms remain unknown [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…MNX1 antisense RNA 1 (MNX1-AS1) was firstly discovered as a highly expressed gene in colorectal malignant tumor, which is termed CCAT5 as well [12]. Recently, a growing number of studies suggested that MNX1-AS1 was aberrantly expressed in diverse malignancies, including cholangiocarcinoma [13], esophagus cancer [14], breast carcinoma [15][16][17], gastric carcinoma [12,18,19], bladder carcinoma [20], ovarian carcinoma [21,22], cervical cancer [23], osteosarcoma [24,25], laryngeal cancer [26], lung cancer [27][28][29], prostate cancer [30], hepatocellular carcinoma [15], glioblastoma [31] and colon adenocarcinoma [32]. Moreover, aberrant MNX1-AS1 expression has been proposed to correlated with cancer patient survival, indicating its potential as prognostic marker and therapeutic target [12,15,18,23,26].…”

Section: Introductionmentioning

confidence: 99%

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Clinical significance of long noncoding RNA MNX1-AS1 in human cancers: a meta-analysis of cohort studies and bioinformatics analysis based on TCGA datasets

et al. 2021

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MNX1-AS1 expression has been proposed to be abnormally upregulated in multiple human malignancies and be linked with the survival outcome of patients. However, relevant conclusions were yielded based on the limited samples. Therefore, we herein implemented a meta-analysis of the published cohort studies to further decipher the relationship of MNX1-AS1 level to prognosis and clinicopathological features in various cancers. Additionally, using The Cancer Genome Atlas (TCGA) datasets we carried out a bioinformatics analysis to make a further evaluation on the prognostic value of MNX1-AS1 expression. The results of meta-analysis indicated elevated MNX1-AS1 level closely correlated with poorer overall survival (OS) (HR = 1.97, 95% CI, 1.73-2.24; P < 0.00001), and disease-free survival (DFS) (HR = 2.24, 95% CI, 1.48-3.38; P = 0.0001) in cancers, which was confirmed by the bioinformatics analysis. Besides, it was observed the upregulated MNX1-AS1 level was significantly related to invasion depth, disease stage, tumor metastasis, and differentiation. Collectively, high MNX1-AS1 level correlated with poor survival outcome and aggressive clinicopathological characteristics in various cancers, suggesting that MNX1-AS1 may be applied as a prognostic marker and even a therapeutic target. Nevertheless, more high-quality studies designed with a large sample size should be conducted to further determine the clinical role of MNX1-AS1 in specific cancer types.

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“…Recently, accumulating reports have revealed that lncRNAs act as tumor facilitators and suppressors, thereby affecting the development of tumors [8,9]. For example, long non-coding RNA MNX1-AS1 promotes TNBC development by enhancing phosphorylation of Stat3 [10]. PCAT6 promotes TNBC cell proliferation, migration, invasion, and EMT [11].…”

Section: Introductionmentioning

confidence: 99%

The LINC00504/Mir-4739/KLK4 Axis Facilitates Cell Proliferation and Suppresses Cell Apoptosis Through Triggering The Wnt/Β-Catenin Pathway In Triple-Negative Breast Cancer Cells

Wu¹,

Jia²,

Zhang³

et al. 2020

Preprint

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Background: Currently, long non-coding RNAs (lncRNAs) have been validated to exert critical influence on the malignant progression of triple-negative breast cancer (TNBC). LncRNA long intergenic non-protein coding RNA 504 (LINC00504) has been recently reported as a tumor facilitator in the cellular processes of several cancers. However, its function in TNBC remains unknown.Methods: CCK-8 and colony formation assays were used to detect the cell viability and proliferation in TNBC. Flow cytometry analysis was utilized to measure the cycle and apoptosis of TNBC cells. The levels of key proteins associated with cell apoptosis or the β-catenin pathway were detected through western blot analysis. The activity of the Wnt/β-catenin signaling pathway was measured by the TOP/FOP flash assay. ChIP assay was conducted to confirm the binding between LINC00504 and its transcription factor signal transducer and activator of transcription 3 (STAT3). RIP and luciferase reporter assays were used to detect and verify the interaction among LINC00504 and its downstream molecule.Results: LncRNA LINC00504 was upregulated in TNBC, and silenced LINC00504 suppressed cell proliferation and triggers cell cycle arrest at G0/G1 stage and cell apoptosis in TNBC cells. STAT3 can transcriptionally activate LINC00504 and LINC00504 served as a molecular sponge of microRNA (miR-4379). Kallikrein related peptidase 4 (KLK4) was the target gene of miR-4379 and activates the Wnt/β-catenin pathway. LINC00504 upregulated KLK4 via competitively binding with miR-4379 to activate the Wnt/β-catenin pathway in TNBC. The suppression on TNBC cell proliferation and the promotion on TNBC cell cycle arrest and apoptosis under LINC00504 knockdown were rescued by miR-4379 depletion or KLK4 overexpression.Conclusions: The LINC00504/miR-4379/KLK4 axis promotes cell growth and cell cycle progression as well as suppresses cell apoptosis through activating the Wnt/β-catenin pathway.

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Long Non-Coding RNA MNX1-AS1 Promotes Progression of Triple Negative Breast Cancer by Enhancing Phosphorylation of Stat3

Cited by 22 publications

References 22 publications

The lncRNA ADAMTS9-AS2 Regulates RPL22 to Modulate TNBC Progression via Controlling the TGF-β Signaling Pathway

The lncRNA ADAMTS9-AS2 Regulates RPL22 to Modulate TNBC Progression via Controlling the TGF-β Signaling Pathway

Clinical significance of long noncoding RNA MNX1-AS1 in human cancers: a meta-analysis of cohort studies and bioinformatics analysis based on TCGA datasets

The LINC00504/Mir-4739/KLK4 Axis Facilitates Cell Proliferation and Suppresses Cell Apoptosis Through Triggering The Wnt/Β-Catenin Pathway In Triple-Negative Breast Cancer Cells

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