Robust expression of tumor suppressor miRNA’s let-7 and miR-195 detected in plasma of Saudi female breast cancer patients

Abstract

BackgroundFemale breast cancer is frequently diagnosed at a later stage and the leading cause of cancer deaths world-wide. Levels of cell-free circulating microRNAs (miRNAs) can potentially be used as biomarkers to measure disease progression in breast cancer patients in a non-invasive way and are therefore of high clinical value.MethodsUsing quantitative RT-PCR, circulating miRNAs were measured in blood samples collected from disease-free individuals (n = 34), triple-negative breast tumours (TNBC) (n = 36) and luminal tumours (n = 57). In addition to intergroup comparisons, plasma miRNA expression levels of all groups were analyzed against RNASeq data from cancerous breast tissue via The Cancer Genome Atlas (TCGA).ResultsA differential set of 18 miRNAs were identified in the plasma of breast cancer patients and 10 miRNAs were uniquely identified based on ROC analysis. The most striking findings revealed elevated tumor suppressor let-7 miRNA in luminal breast cancer patients, irrespective of subtype, and elevated miR-195 in plasma of TNBC breast cancer patients. In contrast, hsa-miR-195 and let-7 miRNAs were absent from cancerous TCGA tissue and strongly expressed in surrounding non-tumor tissue indicating that cancerous cells may selectively export tumor suppressor hsa-miR-195 and let-7 miRNAs in order to maintain oncogenesis.ConclusionsWhile studies have indicated that the restoration of let-7 and miR-195 may be a potential therapy for cancer, these results suggested that tumor cells may selectively export hsa-miR-195 and let-7 miRNAs thereby neutralizing their potential therapeutic effect. However, in order to facilitate earlier detection of breast cancer, blood based screening of hsa-miR-195 and let-7 may be beneficial in a female patient cohort.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3776-5) contains supplementary material, which is available to authorized users.

miR‐188‐5p suppresses cellular proliferation and migration via IL6ST: A potential noninvasive diagnostic biomarker for breast cancer

“…For example, miR-92a was found to be overexpressed in hepatocellular carcinoma tissues and to promote cancer cell proliferation, whereas its levels were decreased in the plasma of patients with hepatocellular carcinoma as relative to healthy individuals (Shigoka et al, 2010). Similarly, the tumor suppressors let-7 and miR-195 were undetectable in breast cancer tissues, whereas they were elevated in breast cancer patient plasma (Qattan et al, 2017). Thus, it can be seen that circulating miRNA levels do not necessarily reflect their tissue levels and functional roles (Cookson et al, 2012).…”

Long noncoding RNA ZFAS1 enhances adriamycin resistance in pediatric acute myeloid leukemia through the miR-195/Myb axis

“…Among these candidates, miR-195 was of interest in this research owing to its tumor suppressive role in a series of human cancers, such as breast cancer, bladder cancer and prostate cancer. [28][29][30] Subsequently, we rstly validated that ZFAS1 directly targeted miR-195 and inhibited miR-195 expression. Previous researches reported that miR-195 signicantly alleviated cancer cell resistance to chemotherapy in colorectal cancer and gastric cancer.…”

Duplicitous Dispositions of Micro-RNAs (miRs) in Breast Cancer

“…In addition to upregulation of oncogenic miRNAs, tumor suppressor Let-7c was decreased in BC tissue and sera according to a study performed in China (n = 90 BC, n = 64 controls) [103]. Although some studies have suggested that let-7 and miR-195 restoration may be therapeutic, results of Qattan et al in 2017 [104] supported literature indicating that tumor cells export hsa-miR-195 and let-7 miRNAs. While the data of this study did not generally support the use of these miRNAs as therapies, it suggested that these markers may be the most robust markers to use in a blood-based screen for the early detection of TNBC and luminal breast cancer [104].…”

“…Although some studies have suggested that let-7 and miR-195 restoration may be therapeutic, results of Qattan et al in 2017 [104] supported literature indicating that tumor cells export hsa-miR-195 and let-7 miRNAs. While the data of this study did not generally support the use of these miRNAs as therapies, it suggested that these markers may be the most robust markers to use in a blood-based screen for the early detection of TNBC and luminal breast cancer [104]. The definition of a prognostic biomarker is one that indicates recurrence or progression; such as chance of survival, independent of the course of therapy.…”