Inhibition of super enhancer downregulates the expression of KLF5 in basal-like breast cancers

Chen, Chuan-Huizi; Yang, Nong; Zhang, Yongchang; Ding, Jian; Zhang, Wenjuan; Liu, Rong; Li, Wen; Chen, Ceshi

doi:10.7150/ijbs.35138

Cited by 30 publications

(31 citation statements)

References 45 publications

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“…As for its potential clinical application, Chipumuro et al found cyclin-dependent kinase 7 (CDK7) inhibitor, THZ1, selectively downregulates SE-regulated MYCN overexpression and MYCN-driven transcription amplification in neuroblastoma (91). Similarly, other researchers revealed THZ1 suppressed SE-driven oncogenic transcriptional amplification in other cancers (92, 93).…”

Section: Crosstalk Between Sernas and Immune Checkpointsmentioning

confidence: 55%

From Super-Enhancer Non-coding RNA to Immune Checkpoint: Frameworks to Functions

Shen

2019

Front. Oncol.

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Super-enhancers (SEs) are clusters of enhancers that play a key role in regulating genes that determine cell identity. Enhancer RNAs (eRNAs) are non-coding RNAs transcribed from enhancers that function to promote the enhancer's functions via multiple mechanisms, such as recruiting transcription factors to specific enhancers, promoting enhancer-promoter looping, directing chromatin accessibility, interacting with RNA polymerase II and facilitating histone acetylation. Understanding how super-enhancer RNAs (seRNAs) contribute to specific gene regulation has thus become an area of active interest. Immune checkpoint deregulation is one of the key characteristics of tumors and autoimmune diseases, and is also closely related to cell identity. Recent studies revealed a potential pathway for seRNA's involvement in regulating the expression of immune checkpoints. The present study reviews the current knowledge of eRNA function, immune checkpoint blockage mechanism, and its effect. In addition, for the first time, we explore the direct and indirect roles of seRNAs in regulating immune checkpoint expression in cancer and autoimmune diseases.

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Section: Crosstalk Between Sernas and Immune Checkpointsmentioning

confidence: 55%

From Super-Enhancer Non-coding RNA to Immune Checkpoint: Frameworks to Functions

Shen

2019

Front. Oncol.

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“…Previous studies indicated that many KLFs are involved in the development of breast cancer. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] In this study, using in silico analyses, we found that KLF16 might have tumor-promoting roles in breast cancer. KLF16 was first identified as a dopamine receptorregulating factor involved in the regulation of dopamine transmission in the brain.…”

Section: Discussionmentioning

confidence: 97%

“…In basal-like breast cancer, a super-enhancer drives KLF5 upregulation, which subsequently drives cell proliferation, migration, and stemness. 15 On the other hand, in estrogen receptorpositive (ER+) breast cancer, KLF5 inhibits cell proliferation by suppressing the transcriptional activity of ERα. 16 KLF6 inhibits estrogen receptor-mediated breast cancer cell growth via a c-Src-mediated pathway.…”

Section: Introductionmentioning

confidence: 99%

<p>The Clinical Relevance and Function of Krüppel-Like Factor 16 in Breast Cancer</p>

Bang¹,

Li²,

Zhang³

et al. 2020

CMAR

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Background: Krüppel-like factor 16 (KLF16), a member of the KLF family, is involved in metabolism and regulation of the endocrine system and has emerging roles in tumor progression. However, the expression of KLF16 and its role in breast cancer are elusive. Methods: We investigated the expression and prognostic value of KLFs in breast cancer using data acquired from the TCGA BRCA dataset and the Kaplan-Meier plotter dataset. The protein levels of KLF16 in breast specimens were detected by immunohistochemistry (IHC). KLF16 silencing using shRNAs was performed to explore the effects of KLF16 on breast cancer cell growth, migration, and invasion. The expression of EMT markers in cells manipulated for KLF16 expression was assessed by Western blotting. Results: Using publicly available dataset and specimens from breast cancer patients, we found that the expression levels of KLF16 were significantly higher in tumor tissues and that high levels of KLF16 were associated with poor prognosis in breast cancer patients. Moreover, KLF16 expression levels had relation to several clinicopathological parameters of breast cancer, including the molecular subtype and histological grade. Importantly, knockdown of KLF16 dramatically suppressed cell proliferation both in vitro and in vivo. Also, KLF16 deletion impaired migration, and invasion in breast cancer cells, and suppressed epithelial-mesenchymal transition (EMT). Conclusion: Our results suggest that KLF16 has important oncogenic functions in breast cancer and that the expression levels of KLF16 are associated with prognosis in breast cancer patients. Our findings also suggest that KLF16 is involved in proliferation, migration, and invasion in breast cancer cells. Thus, KLF16 might be a promising prognostic marker and a therapeutic target for breast cancer.

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“…The lentiviral pCDH-AKT plasmid was kindly provided by Dr. Binghui Li (Capital Medical University, Beijing, China), and lentiviruses were prepared according to published protocols 30 . MDA-MB-468 cells were infected with lentiviruses and the infected cells were selected by 1 µg/ml puromycin and were used for further analysis.…”

Section: Methodsmentioning

confidence: 99%

Isochromanoindolenines suppress triple-negative breast cancer cell proliferation partially via inhibiting Akt activation

Jiang¹,

Zhi²,

Zhang³

et al. 2021

Int. J. Biol. Sci.

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As the most malignant subtype of breast cancers, triple-negative breast cancer (TNBC) lacks effective targeted therapeutics clinically to date. In this study, one lead compound FZU-0025-065 with isochromanoindolenine scaffold was identified by a cell-based screening. Among nine breast cancer cell lines tested, TNBC are the most sensitive cell lines to FZU-0025-065. FZU-0025-065 inhibits TNBC cell growth in a time-and dosage-dependent manner. FZU-0025-065 suppresses the expression of cell cycle dependent kinase 4 (CDK4), Cyclin D1 and Cyclin B1; meanwhile, elevates the expression of cell cycle dependent kinase inhibitor p21 and p27. Importantly, we found that FZU-0025-065 suppresses AKT activation in a time-and dosage-dependent manner. Over-expression of constitutive active AKT partially rescues FZU-0025-065 induced cell growth inhibition in MDA-MB-468 cells, indicating FZU-0025-065 suppresses TNBC cell growth partially via inhibiting AKT activation. Finally, FZU-0025-065 suppresses TNBC cell growth in a xenograft mouse model. Taken together, our findings suggested that isochromanoindolenine derivative FZU-0025-065 inhibits TNBC via suppressing the AKT signaling and that FZU-0025-065 may be useful for TNBC treatment.

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Inhibition of super enhancer downregulates the expression of KLF5 in basal-like breast cancers

Cited by 30 publications

References 45 publications

From Super-Enhancer Non-coding RNA to Immune Checkpoint: Frameworks to Functions

From Super-Enhancer Non-coding RNA to Immune Checkpoint: Frameworks to Functions

<p>The Clinical Relevance and Function of Krüppel-Like Factor 16 in Breast Cancer</p>

Isochromanoindolenines suppress triple-negative breast cancer cell proliferation partially via inhibiting Akt activation

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