Long non-coding RNA CCAT2 promotes oncogenesis in triple-negative breast cancer by regulating stemness of cancer cells

Xu, Zhen; Liu, Cuiui; Zhao, Qian; Lu, Jianrong; Ding, Xin; Luo, An; He, Jia; Wang, Guangxue; Li, Yuan; Cai, Zhaoqing; Wang, Zhongrui; Liu, Junjun; Liu, Suling; Li, Wenshu; Yu, Zuoren

doi:10.1016/j.phrs.2020.104628

Cited by 60 publications

(47 citation statements)

References 41 publications

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“…An increasing number of studies have revealed the regulatory functions of lncRNAs in the progression of cancer, including TNBC [30]. For example, lncRNABORG facilitates the survival and chemoresistance of TNBC [31], while lncRNA CCAT2 promotes TNBC oncogenesis by regulating the stemness of cancer cells [7]. In addition, LINC01638activates MTDH-Twist1 signalling in TNBC [32].…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA MIR100HG promotes the migration, invasion and proliferation of triple-negative breast cancer cells by targeting the miR-5590-3p/OTX1 axis

et al. 2020

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Background As an aggressive subtype of breast cancer with a high risk of recurrence, triple-negative breast cancer (TNBC) lacks available treatment targets. LncRNA MIR100HG promotes cell proliferation in TNBC. However, few studies have investigated the molecular mechanism of MIR100HG in TNBC. Thus, additional in-depth investigations are needed to unravel its associated regulatory mechanism. Methods MIR100HG and miR-5590-3p expression in TNBC tissue samples and cell lines was detected by RT-qPCR. Flow cytometry, transwell, wound-healing, CCK8 and colony formation assays were performed to analyse cell apoptosis, cell cycle, invasion, migration and proliferation. The protein expression of orthodenticle homeobox 1 (OTX1) and proteins in the ERK/MAPK signalling pathway were assessed by western blot analysis. Bioinformatics and luciferase assay were performed to predict and validate the interaction between MIR100HG and miR-5590-3p as well as OTX1 and miR-5590-3p. RNA immunoprecipitation (RIP) was used to detect the interaction between MIR100HG and miR-5590-3p. Subcutaneous tumour growth was observed in nude mice. Immunohistochemistry (IHC) analysis was used to assess OTX1 expression in tumour tissues. Results MIR100HG expression was upregulated, whereas that of miR-5590-3p was downregulated in TNBC. MIR100HG was shown to directly interact with miR-5590-3p. Furthermore, MIR100HG knockdown could promote TNBC cell apoptosis and cell cycle arrest in G0/G1 phase while inhibiting migration, invasion and proliferation. Furthermore, miR-5590-3p inhibition showed the opposite results and could reverse the effect of MIR100HG knockdown in TNBC cells. MiR-5590-3p downregulated the ERK/MAPK signalling pathway, suppressed the migration, invasion and proliferation of TNBC cells and promoted their apoptosis and cell cycle arrest in G0/G1 phase by targeting OTX1. In addition, MIR100HG knockdown inhibited OTX1 expression by upregulating miR-5590-3p in vivo, thereby inhibiting tumour growth. Conclusions MIR100HG promotes the progression of TNBC by sponging miR-5590-3p, thereby upregulating OTX1, suggesting a new potential treatment target for TNBC.

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Section: Discussionmentioning

confidence: 99%

Long non-coding RNA MIR100HG promotes the migration, invasion and proliferation of triple-negative breast cancer cells by targeting the miR-5590-3p/OTX1 axis

et al. 2020

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“…OCT4 binds to the lncRNA NETA1.1 promoter in human bladder cancer-resistant cells treated with cisplatin, making it highly expressed to maintain the invasion and growth of bladder cancer cells (45). LncRNA CCAT2 overexpressed in human breast CSCs maintains the aggressiveness of CSCs by up-regulating the OCT4 pseudogene (OCT4-PG1) (46). The ability of MALAT1 to maintain the stemness of human colon CSCs may be achieved by targeted inhibition of miR-20b-5p and reducing the binding of miR-20b-5p to OCT4 mRNA (Pou5f1) (47).…”

Section: Non-coding Rna Related To Oct4mentioning

confidence: 99%

The Role and Specific Mechanism of OCT4 in Cancer Stem Cells: A Review

Zhang

Han

Zhu

et al. 2020

IJSC

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Recently, evidences show that cancer stem cells (CSCs) are a type of cancer cell group with self-renewal and play a huge role in tumor recurrence, metastasis, and drug resistance. Finding new treatment directions and targets for cancer prognosis and reducing mortality has become a top priority. OCT4, as a transcription factor, participates in maintaining the stem characteristics of CSCs, but the mechanism of OCT4 is often overlooked. In this review, we try to illustrate the mechanism by which OCT4 plays a role in CSCs from the perspective of genetic modification of OCT4, non-coding RNA, complexes and signaling pathways associated with OCT4. Our ultimate goal is to provide new targets for cancer treatment to prolong the survival of cancer patients.

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“…Because of the findings of activated stem cell pathways from c-Met/β1 complex formation ( Figure 1E) and because breast cancer stem cells have been shown to be a subset of breast cancer cells with enriched metastatic capacity (12), we then asked whether the ability of the c-Met/β1 complex to drive metastases (7) reflected an ability of the complex to enrich the breast cancer stem cell population. Indeed, AP21967 increased the expression of stem cell genes c-Myc (13), Klf4 (14), Oct4 (13), Sox2 (13), and Nanog (13) in MDA-MB-231-iDimerize-c-Met-β1 cells (P<0.001; Figure 1F; Supplemental Figure 5). Consistent with this gene expression profile, AP21967 also doubled the CD44 + CD24stem cell fraction (15) of MDA-MB-231-iDimerize-c-Met-β1 cells (P<0.001; Figure 1G; Supplemental Figure 6).…”

Section: The C-met/β1 Complex Enriches the Stem Cell Fraction In Breamentioning

confidence: 99%

Role of c-Met/β1 integrin complex in the metastatic cascade

Lau

Wadhwa

Sudhir

et al. 2020

Preprint

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Metastases cause 90% of human cancer deaths. The metastatic cascade involves local invasion, intravasation, extravasation, metastatic site colonization, and proliferation.While individual mediators of these processes have been investigated, interactions between these mediators remain less well defined. We previously identified a structural complex between receptor tyrosine kinase c-Met and β1 integrin in metastases. Using novel cell culture and in vivo assays, we found that c-Met/β1 complex induction promotes breast cancer intravasation and adhesion to the vessel wall, but does not increase extravasation. These effects may be driven by the ability of the c-Met/β1 complex to increase mesenchymal and stem cell characteristics. Multiplex transcriptomic analysis revealed upregulated Wnt and hedgehog pathways after c-Met/β1 complex induction. A β1 integrin point mutation that prevented binding to c-Met reduced intravasation. OS2966, a therapeutic antibody disrupting c-Met/β1 binding, decreased invasion and mesenchymal gene expression and morphology of breast cancer cells. Bone-seeking breast cancer cells exhibited higher c-Met/β1 complex levels than parental controls and preferentially adhere to tissue-specific matrix. Patient bone metastases demonstrated higher c-Met/β1 levels than brain metastases. Thus, the c-Met/β1 complex drives breast cancer cell intravasation and preferential affinity for bone tissue-specific matrix.Pharmacological targeting of the complex may prevent metastases, particularly osseous metastases.

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Long non-coding RNA CCAT2 promotes oncogenesis in triple-negative breast cancer by regulating stemness of cancer cells

Cited by 60 publications

References 41 publications

Long non-coding RNA MIR100HG promotes the migration, invasion and proliferation of triple-negative breast cancer cells by targeting the miR-5590-3p/OTX1 axis

Long non-coding RNA MIR100HG promotes the migration, invasion and proliferation of triple-negative breast cancer cells by targeting the miR-5590-3p/OTX1 axis

The Role and Specific Mechanism of OCT4 in Cancer Stem Cells: A Review

Role of c-Met/β1 integrin complex in the metastatic cascade

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