Tumor Suppressor miR-27a-5p and Its Significance for Breast Cancer.

MicroRNAs are well established as master regulators of carcinogenesis and potential biomarkers in breast cancer (BC). In a preliminary effort, we found miR-27a-5p to be significantly downregulated in experimentally derived mammospheres and BC patients from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) dataset. Herein, we sought to investigate the putative involvement of miR-27a-5p in promoting a migratory phenotype of breast cancer cells, and establish whether miR-27a-5p is associated with patient clinicopathological characteristics.

E2F transcription factor-1 modulates expression of glutamine metabolic genes in mouse embryonic fibroblasts and uterine sarcoma cells.

Metabolic reprogramming is considered as a hallmark of cancer and is clinically exploited as a novel target for therapy. The E2F transcription factor-1 (E2F1) regulates various cellular processes, including proliferative and metabolic pathways, and acts, depending on the cellular and molecular context, as an oncogene or tumor suppressor. The latter is evident by the observation that E2f1-knockout mice develop spontaneous tumors, including uterine sarcomas.

MiR-4646-5p Acts as a Tumor-Suppressive Factor in Triple Negative Breast Cancer and Targets the Cholesterol Transport Protein GRAMD1B.

MicroRNAs (miRNAs) are crucial post-transcriptional regulators of gene expression, and their deregulation contributes to many aspects of cancer development and progression. Thus, miRNAs provide insight into oncogenic mechanisms and represent promising targets for new therapeutic approaches. A type of cancer that is still in urgent need of improved treatment options is triple negative breast cancer (TNBC).

MicroRNAs as regulators of tumor metabolism.

Cancer cells reprogram their metabolism to support their growth. Since the discovery of the Warburg effect, several other metabolic alterations and metabolites have been described in cancer cells, including lactate, glutamine, and lipid metabolism reprogramming. Together these alterations provide rapidly dividing tumor cells with metabolic intermediates needed for nucleotide, protein, and fatty acid biosynthesis.

MicroRNA mimics can distort physiological microRNA effects on immune checkpoints by triggering an antiviral interferon response.

The microRNA-200 family has wide-ranging regulatory functions in cancer development and progression. Above all, it is strongly associated with the epithelial-to-mesenchymal transition (EMT), a process during which cells change their epithelial to a mesenchymal phenotype and acquire invasive characteristics. More recently, miR-200 family members have also been reported to impact the immune evasion of cancer cells by regulating the expression of immunoinhibitory immune checkpoints (ICs) like PD-L1.

ALYREF, a novel factor involved in breast carcinogenesis, acts through transcriptional and post-transcriptional mechanisms selectively regulating the short NEAT1 isoform.

The RNA-binding protein ALYREF (THOC4) is involved in transcriptional regulation and nuclear mRNA export, though its role and molecular mode of action in breast carcinogenesis are completely unknown. Here, we identified high ALYREF expression as a factor for poor survival in breast cancer patients. ALYREF significantly influenced cellular growth, apoptosis and mitochondrial energy metabolism in breast cancer cells as well as breast tumorigenesis in orthotopic mouse models.

MiR-200c-3p Modulates Cisplatin Resistance in Biliary Tract Cancer by ZEB1-Independent Mechanisms.

Biliary tract cancer is a major global health issue in cancer-related mortality. Therapeutic options are limited, and cisplatin-based treatment schedules represent the mainstay of first-line therapeutic strategies. Although the gain of survival by the addition of cisplatin to gemcitabine is moderate, acquired cisplatin resistance frequently leads to treatment failures with mechanisms that are still poorly understood.

Involvement of Long Non-Coding RNAs (lncRNAs) in Tumor Angiogenesis.

Long non-coding RNAs (lncRNAs) are defined as non-protein coding transcripts with a minimal length of 200 nucleotides. They are involved in various biological processes such as cell differentiation, apoptosis, as well as in pathophysiological processes. Numerous studies considered that frequently deregulated lncRNAs contribute to all hallmarks of cancer including metastasis, drug resistance, and angiogenesis.

Long-Noncoding RNA (lncRNA) in the Regulation of Hypoxia-Inducible Factor (HIF) in Cancer.

Hypoxia is dangerous for oxygen-dependent cells, therefore, physiological adaption to cellular hypoxic conditions is essential. The transcription factor hypoxia-inducible factor (HIF) is the main regulator of hypoxic metabolic adaption reducing oxygen consumption and is regulated by gradual von Hippel-Lindau (VHL)-dependent proteasomal degradation. Beyond physiology, hypoxia is frequently encountered within solid tumors and first drugs are in clinical trials to tackle this pathway in cancer.

RNA-Binding Proteins as Important Regulators of Long Non-Coding RNAs in Cancer.

The majority of the genome is transcribed into pieces of non-(protein) coding RNA, among which long non-coding RNAs (lncRNAs) constitute a large group of particularly versatile molecules that govern basic cellular processes including transcription, splicing, RNA stability, and translation. The frequent deregulation of numerous lncRNAs in cancer is known to contribute to virtually all hallmarks of cancer. An important regulatory mechanism of lncRNAs is the post-transcriptional regulation mediated by RNA-binding proteins (RBPs).