ABSTRACT
Breast cancer ranks as the most prevalent cancer globally, surpassing lung cancer, with recurrence/metastasis to be its main account for the cancer-related mortality. MicroRNAs (miRNAs) participate critically in various physiological and pathological processes through posttranscriptional regulation of downstream genes. Our preliminary findings identified miR-338-5p, potentially linked to metastasis in breast cancer, a previously unexplored area. Analysis of the GSE38867 dataset revealed the decreased miR-338-5p expression in metastatic breast cancer compared to normal tissues. Cellular function experiments and a xenograft tumor model demonstrated the inhibitory function of miR-338-5p on the progression of breast cancer in vitro and in vivo. Furthermore, it downregulated the expression of mesenchymal biomarkers and NOTCH1 significantly. With the predicting targets of miR-338-5p and transcription factors of the NOTCH1 gene, coupled with dual luciferase reporter assays, it is identified ETS1 as the interactor between miR-338-5p and NOTCH1. In breast cancer tissues, as well as in our xenograft tumor model, expression of ETS1 and NOTCH1 was positively correlated using immunohistochemical staining. This study reports, for the first time, on the miR-338-5p/ETS1/NOTCH1 axis and its pivotal role in breast cancer proliferation and metastasis. These findings propose a novel therapeutic strategy for breast cancer patients and lays a foundation for its clinical detection and treatment evaluation.
ABSTRACT
Small nucleolar RNAs (snoRNAs) represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification, thereby contributing significantly to the maintenance of cellular functions related to protein synthesis. SnoRNAs have been discovered to possess the ability to influence cell fate and alter disease progression, holding immense potential in controlling human diseases. It is suggested that the dysregulation of snoRNAs in cancer exhibits differential expression across various cancer types, stages, metastasis, treatment response and/or prognosis in patients. On the other hand, colorectal cancer (CRC), a prevalent malignancy of the digestive system, is characterized by high incidence and mortality rates, ranking as the third most common cancer type. Recent research indicates that snoRNA dysregulation is associated with CRC, as snoRNA expression significantly differs between normal and cancerous conditions. Consequently, assessing snoRNA expression level and function holds promise for the prognosis and diagnosis of CRC. Nevertheless, current comprehension of the potential roles of snoRNAs in CRC remains limited. This review offers a comprehensive survey of the aberrant regulation of snoRNAs in CRC, providing valuable insights into the discovery of novel biomarkers, therapeutic targets, and potential tools for the diagnosis and treatment of CRC and furnishing critical cues for advancing research into CRC and the judicious selection of therapeutic targets.
Subject(s)
Colorectal Neoplasms , RNA, Small Nucleolar , Humans , RNA, Small Nucleolar/genetics , RNA, Small Nucleolar/metabolism , Carcinogenesis/genetics , Cell Transformation, Neoplastic/genetics , Prognosis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathologyABSTRACT
Chronic inflammation is known to increase the risk of gastrointestinal cancers (GICs), the common solid tumors worldwide. Precancerous lesions, such as chronic atrophic inflammation and ulcers, are related to inflammatory responses in vivo and likely to occur in hyperplasia and tumorigenesis. Unfortunately, due to the lack of effective therapeutic targets, the prognosis of patients with GICs is still unsatisfactory. Interestingly, it is found that six transmembrane epithelial antigens of the prostate (STEAPs), a group of metal reductases, are significantly associated with the progression of malignancies, playing a crucial role in systemic metabolic homeostasis and inflammatory responses. The structure and functions of STEAPs suggest that they are closely related to intracellular oxidative stress, responding to inflammatory reactions. Under the imbalance status of abnormal oxidative stress, STEAP members are involved in cell transformation and the development of GICs by inhibiting or activating inflammatory process. This review focuses on STEAPs in GICs along with exploring their potential molecular regulatory mechanisms, with an aim to provide a theoretical basis for diagnosis and treatment strategies for patients suffering from these types of cancers.