Breast cancer represents a major health burden in Europe and North America, as recently published data report breast cancer as the second leading cause of cancer related death in women worldwide. Breast cancer is regarded as a highly heterogeneous disease in terms of clinical course and biological behavior and can be divided into several molecular subtypes, with different prognosis and treatment responses. The discovery of numerous non-coding RNAs has dramatically changed our understanding of cell biology, especially the pathophysiology of cancer. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts >200 nucleotides in length. Several studies have demonstrated their role as key regulators of gene expression, cell biology and carcinogenesis. Deregulated expression levels of lncRNAs have been observed in various types of cancers including breast cancer. lncRNAs are involved in cancer initiation, progression, and metastases. In this review, we summarize the recent literature to highlight the current status of this class of long non-coding lncRNAs in breast cancer.

miR-196b-5p has been previously implicated in malignant transformation; however, its role in colorectal cancer has not been fully explored. In this study, we examine the clinical and biological relevance of miR-196b-5p, and the molecular pathways regulated by miR-196b-5p in colorectal cancer. miR-196b-5p expression was quantitated by qRT-PCR in 2 independent cohorts composed of 292 patients with colorectal cancer in total, to explore its biomarker potential. Transient and stable gain- and loss-of-function experiments were conducted in a panel of colorectal cancer cell lines and mice, to evaluate the impact of miR-196b-5p on proliferation, chemosensitivity, migration/invasion, and metastases formation and The molecular pathways influenced by miR-196b-5p were characterized using whole transcriptome profiling, target prediction tools, luciferase interaction assays, and phenocopy/rescue gene knockdown experiments. Low miR-196b-5p expression was significantly associated with metastases and poor outcomes in 2 independent colorectal cancer patient cohorts ( < 0.05, log-rank test). miR-196b-5p inhibition led to significantly increased colorectal cancer cell migration/invasion and metastases formation in mice, whereas ectopic overexpression showed the opposite phenotype. Molecular profiling and target confirmation identified an interaction between miR-196b-5p and and which in turn regulated colorectal cancer cell migration. The association of low levels of miR-196b-5p and poor prognosis in patients with colorectal cancer can be explained by its influence on cancer cell migration and metastases formation. miR-196b-5p has an impact on colorectal cancer progression pathways through direct interaction with genes involved in cancer cell migration. .

SOX9 has been previously shown to be involved in hepatocellular carcinoma (HCC) and other types of cancer. However, prognostic studies so far involved rather small cohorts or lack external validation and experimental data. In this study, we firstly determined the histological expression pattern of SOX9 in human HCC by immunohistochemistry (n = 84) and evaluated its prognostic value. External cohorts of publicly available datasets were used to validate its prognostic relevance in HCC (n = 359) and other types of cancer including breast (n = 3951), ovarian (n = 1306), lung (n = 1926) and gastric cancer (n = 876). Functional SOX9 knock-down studies using siRNA and cancer stem cell models were generated in a panel of liver and breast cancer cell lines. High level of SOX9 was associated with poor survival even after adjustment for other prognostic factors in multivariate analysis (HR = 2.103, 95%CI = 1.064 to 4.156, p = 0.021). SOX9 prevailed a poor prognostic factor in all cancer validation cohorts (p<0.05). Reduced SOX9 expression by siRNA decreased the growth of liver cancer cells (p<0.05). SOX9 expression was associated with stem cell features in all tested cell lines (p<0.05). In conclusion, this study demonstrated in a large number of patients from multiple cohorts that high levels of SOX9 are a consistent negative prognostic factor.

Metastatic testicular germ cell tumors (TGCTs) are a potentially curable disease by administration of risk-adapted cytotoxic chemotherapy. Nevertheless, a disease-relapse after curative chemotherapy needs more intensive salvage chemotherapy and significantly worsens the prognosis of TGCT patients. Circulating tumor markers (β-subunit of human chorionic gonadotropin (β-HCG), alpha-Fetoprotein (AFP), and Lactate Dehydrogenase (LDH)) are frequently used for monitoring disease recurrence in TGCT patients, though they lack diagnostic sensitivity and specificity. Increasing evidence suggests that serum levels of stem cell-associated microRNAs (miR-371a-3p and miR-302/367 cluster) are outperforming the traditional tumor markers in terms of sensitivity to detect newly diagnosed TGCT patients. The aim of this study was to investigate whether these miRNAs are also informative in detection of disease recurrence in TGCT patients after curative first line therapy. For this purpose, we measured the serum levels of miR-371a-3p and miR-367 in 52 samples of ten TGCT patients at different time points during disease relapse and during salvage chemotherapy. In our study, miR-371a-3p levels in serum samples with proven disease recurrence were 13.65 fold higher than levels from the same patients without evidence of disease (p = 0.014). In contrast, miR-367 levels were not different in these patient groups (p = 0.985). In conclusion, miR-371a-3p is a sensitive and potentially novel biomarker for detecting disease relapse in TGCT patients. This promising biomarker should be investigated in further large prospective trials.

A 52-year-old German female presented with cervical lymphadenopathy and fever. Despite the initial symptom-presentation leading to the consideration of sarcoidosis, lymphoma, tuberculosis, and toxoplasmosis, an extensive serologic and histo- and molecular pathologic workup eventually indicated a likely diagnosis of tularemia. This case brings to light that tularemia is a diagnostic challenge and requires high reliance on the epidemiological context thorough patient history, and an extensive interdisciplinary diagnostic workup.

<p>Supplementary Material</p>

<p>Supplementary Table 1: Primer sequences used for qRT PCR analysis Supplementary Table 2; Summary and comparison of clinico-pathological characteristics of the colorectal cancer patients in cohort 1 (n = 110) and cohort 2 (n = 182). Supplementary table 3 Univariate analysis of clinico-pathological parameters for the prediction of 5-years overall survival in patients with colorectal cancer in cohort 1 (n=110) and cohort 2 (n=182). Supplementary Table 4 Multivariate analysis of clinico-pathological parameters for the prediction of 5-years overall survival in patients with colorectal cancer in cohort 1 (n=110) and cohort 2 (n=182). Supplementary table 5: Up- and downregulated transcripts obtained from a microarray whole transcriptome profiling analysis in three independent biological replicates comparing the HCT116 miR-196b-5p stably overexpressing cells against control cells Supplementary Table 6: Down-regulated genes identified in the microarray analysis underwent in silico target prediction analysis according to the details described in the methods section. The table shows only downregulated genes with potentially miR-196b-5p interaction sites.</p>

<p>Supplementary Figure Legend</p>