MicroRNA-138 is a Prognostic Biomarker for Triple-Negative Breast Cancer and Promotes Tumorigenesis via TUSC2 repression

Nama, Srikanth; Muhuri, Manish; Pascale, Federica Di; Quah, Shan; Aswad, Luay; Fullwood, Melissa J.; Sampath, Prabha

doi:10.1038/s41598-019-49155-4

Cited by 36 publications

(31 citation statements)

References 34 publications

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“…MiRNAs are synthesized as double-stranded precursors in the nucleus, cleaved (multiple times, sequentially), and translocated to the cytoplasm. Mature miRNAs are loaded onto Argonaute proteins (AGOs) to produce RNA-induced silencing complexes (RISC) that target messenger RNAs (mRNAs) via partial complementary base pairing in the 3′-untranslated region (3′-UTR) or 5′-UTR [ 18 , 19 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Exosomal MicroRNAs and Organotropism in Breast Cancer Metastasis

Wong

Jalboush

2020

Cancers

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Breast cancer is the most frequent malignancy for women in which one in eight women will be diagnosed with the disease in their lifetime. Despite advances made in treating primary breast cancer, there is still no effective treatment for metastatic breast cancer. Consequently, metastatic breast cancer is responsible for 90% of breast cancer-related deaths while only accounting for approximately one third of all breast cancer cases. To help develop effective treatments for metastatic breast cancer, it is important to gain a deeper understanding of the mechanisms by which breast cancer metastasizes, particularly, those underlying organotropism towards brain, bone, and lungs. In this review, we will primarily focus on the roles that circulating exosomal microRNAs (miRNAs) play in organotropism of breast cancer metastasis. Exosomes are extracellular vesicles that play critical roles in intercellular communication. MicroRNAs can be encapsulated in exosomes; cargo-loaded exosomes can be secreted by tumor cells into the tumor microenvironment to facilitate tumor–stroma interactions or released to circulation to prime distant organs for subsequent metastasis. Here, we will summarize our current knowledge on the biogenesis of exosomes and miRNAs, mechanisms of cargo sorting into exosomes, the exosomal miRNAs implicated in breast cancer metastasis, and therapeutic exosomal miRNAs.

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Section: Introductionmentioning

confidence: 99%

Exosomal MicroRNAs and Organotropism in Breast Cancer Metastasis

Wong

Jalboush

2020

Cancers

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“…It is well established that aberrant expression of miRNAs, a class of short noncoding endogenous RNAs that regulate gene expression by binding to the 3′-untranslated regions of their target mRNAs, fosters cancer development [5]. Several miRNAs have been reported to act as regulators Edited by G Melino of breast cancer development and progression and correlate with the hormone receptor status [6].…”

Section: Introductionmentioning

confidence: 99%

Aberrant transcriptional and post-transcriptional regulation of SPAG5, a YAP-TAZ-TEAD downstream effector, fuels breast cancer cell proliferation

Canu¹,

Donzelli²,

Sacconi³

et al. 2020

Cell Death Differ

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Sperm-associated antigen 5 (SPAG5) is an important driver of the cell mitotic spindle required for chromosome segregation and progression into anaphase. SPAG5 has been identified as an important proliferation marker and chemotherapy-sensitivity predictor, especially in estrogen receptor-negative breast cancer subtypes. Here, we report that SPAG5 is a direct target of miR-10b-3p, and its aberrantly high expression associates with poor disease-free survival in two large cohorts of breast cancer patients. SPAG5 depletion strongly impaired cancer cell cycle progression, proliferation, and migration. Interestingly, high expression of SPAG5 pairs with a YAP/TAZ-activated signature in breast cancer patients. Reassuringly, the depletion of YAP, TAZ, and TEAD strongly reduced SPAG5 expression and diminished its oncogenic effects. YAP, TAZ coactivators, and TEAD transcription factors are key components of the Hippo signaling pathway involved in tumor initiation, progression, and metastasis. Furthermore, we report that SPAG5 is a direct transcriptional target of TEAD/YAP/TAZ, and pharmacological targeting of YAP and TAZ severely reduces SPAG5 expression. Collectively, our data uncover an oncogenic feedback loop, comprising miR-10b-3p, SPAG5, and YAP/TAZ/TEAD, which fuels the aberrant proliferation of breast cancer.

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“…Numerous alterations to miRNAs, such as single-nucleotide polymorphisms (SNPs), methylation, and stabilization, could, in some cases, be pathologically advantageous for the development of cancer [ 268 ]. Importantly, miRNAs could prove invaluable as prognostic and diagnostic biomarkers in a wide variety of cancers, potentially improving our understanding of clinical adversities to treatment and preventative care [ 269 , 270 , 271 ]. Recent explorations continue to pioneer our understanding of the diverse roles of miRNAs and gene silencing in cancer research.…”

Section: Emerging Areas Of Research Involving Pkm2mentioning

confidence: 99%

The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs

Puckett

Alquraishi

Chowanadisai

et al. 2021

IJMS

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Pyruvate kinase is a key regulator in glycolysis through the conversion of phosphoenolpyruvate (PEP) into pyruvate. Pyruvate kinase exists in various isoforms that can exhibit diverse biological functions and outcomes. The pyruvate kinase isoenzyme type M2 (PKM2) controls cell progression and survival through the regulation of key signaling pathways. In cancer cells, the dimer form of PKM2 predominates and plays an integral role in cancer metabolism. This predominance of the inactive dimeric form promotes the accumulation of phosphometabolites, allowing cancer cells to engage in high levels of synthetic processing to enhance their proliferative capacity. PKM2 has been recognized for its role in regulating gene expression and transcription factors critical for health and disease. This role enables PKM2 to exert profound regulatory effects that promote cancer cell metabolism, proliferation, and migration. In addition to its role in cancer, PKM2 regulates aspects essential to cellular homeostasis in non-cancer tissues and, in some cases, promotes tissue-specific pathways in health and diseases. In pursuit of understanding the diverse tissue-specific roles of PKM2, investigations targeting tissues such as the kidney, liver, adipose, and pancreas have been conducted. Findings from these studies enhance our understanding of PKM2 functions in various diseases beyond cancer. Therefore, there is substantial interest in PKM2 modulation as a potential therapeutic target for the treatment of multiple conditions. Indeed, a vast plethora of research has focused on identifying therapeutic strategies for targeting PKM2. Recently, targeting PKM2 through its regulatory microRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) has gathered increasing interest. Thus, the goal of this review is to highlight recent advancements in PKM2 research, with a focus on PKM2 regulatory microRNAs and lncRNAs and their subsequent physiological significance.

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MicroRNA-138 is a Prognostic Biomarker for Triple-Negative Breast Cancer and Promotes Tumorigenesis via TUSC2 repression

Cited by 36 publications

References 34 publications

Exosomal MicroRNAs and Organotropism in Breast Cancer Metastasis

Exosomal MicroRNAs and Organotropism in Breast Cancer Metastasis

Aberrant transcriptional and post-transcriptional regulation of SPAG5, a YAP-TAZ-TEAD downstream effector, fuels breast cancer cell proliferation

The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs

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