Noncoding RNAs: Emerging regulators of behavioral complexity.

The mammalian genome encodes thousands of non-coding RNAs (ncRNAs), ranging in size from about 20 nucleotides (microRNAs or miRNAs) to kilobases (long non-coding RNAs or lncRNAs). ncRNAs contribute to a layer of gene regulation that could explain the evolution of massive phenotypic complexity even as the number of protein-coding genes remains unaltered. We propose that low conservation, poor expression, and highly restricted spatiotemporal expression patterns-conventionally considered ncRNAs may affect behavior through direct, rapid, and often sustained regulation of gene expression at the transcriptional, post-transcriptional, or translational levels. Besides these direct roles, their effect during neurodevelopment may manifest as behavioral changes later in the organism's life, especially when exposed to environmental cues like stress and seasonal changes. The lncRNAs affect behavior through diverse mechanisms like sponging of miRNAs, recruitment of chromatin modifiers, and regulation of alternative splicing. We highlight the need for synthesis between rigorously designed behavioral paradigms in model organisms and the wide diversity of behaviors documented by ethologists through field studies on organisms exquisitely adapted to their environmental niche. Comparative genomics and the latest advancements in transcriptomics provide an unprecedented scope for merging field and lab studies on model and non-model organisms to shed light on the role of ncRNAs in driving the behavioral responses of individuals and groups. We touch upon the technical challenges and contentious issues that must be resolved to fully understand the role of ncRNAs in regulating complex behavioral traits. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.

Immune profile of primary and recurrent epithelial ovarian cancer cases indicates immune suppression, a major cause of progression and relapse of ovarian cancer.

BACKGROUND: Ovarian cancer is the third most prevalent cancer in Indian women. Relative frequency of High grade serous epithelial ovarian cancer (HGSOC) and its associated deaths are highest in India which suggests the importance of understanding their immune profiles for better treatment modality. Hence, the present study investigated the NK cell receptor expression, their cognate ligands, serum cytokines, and soluble ligands in primary and recurrent HGSOC patients. We have used multicolor flow cytometry for immunophenotyping of tumor infiltrated and circulatory lymphocytes. Procartaplex, and ELISA were used to measure soluble ligands and cytokines of HGSOC patients. RESULTS: Among the enrolled 51 EOC patients, 33 were primary high grade serous epithelial ovarian cancer (pEOC) and 18 were recurrent epithelial ovarian cancer (rEOC) patients. Blood samples from 46 age matched healthy controls (HC) were used for comparative analysis. Results revealed, frequency of circulatory CD56Bright NK, CD56Dim NK, NKT-like, and T cells was reduced with activating receptors while alterations in immune subsets with inhibitory receptors were observed in both groups. Study also highlights differential immune profile of primary and recurrent ovarian cancer patients. We have found increased soluble MICA which might have acted as "decoy" molecule and could be a reason of decrease in NKG2D positive subsets in both groups of patients. Furthermore, elevated level of serum cytokines IL-2, IL-5, IL-6, IL-10, and TNF-α in ovarian cancer patients, might be associated with ovarian cancer progression. Profiling of tumor infiltrated immune cells revealed the reduced level of DNAM-1 positive NK and T cells in both groups than their circulatory counterpart, which might have led to decrease in NK cell's ability of synapse formation. CONCLUSIONS: The study brings out differential receptor expression profile on CD56BrightNK, CD56DimNK, NKT-like, and T cells, cytokines levels and soluble ligands which may be exploited to develop alternate therapeutic approaches for HGSOC patients. Further, few differences in the circulatory immune profiles between pEOC and rEOC cases, indicates the immune signature of pEOC undergoes some changes in circulation that might facilitated the disease relapse. They also maintains some common immune signatures such as reduced expression of NKG2D, high level of MICA as well as IL-6, IL10 and TNF-α, which indicates irreversible immune suppression of ovarian cancer patients. It is also emphasized that a restoration of cytokines level, NKG2D and DNAM-1on tumor infiltrated immune cells may be targeted to develop specific therapeutic approaches for high-grade serous epithelial ovarian cancer.

Immune Profile of Blood, Tissue and Peritoneal Fluid: A Comparative Study in High Grade Serous Epithelial Ovarian Cancer Patients at Interval Debulking Surgery.

High-grade serous epithelial ovarian carcinoma (HGSOC) is an immunogenic tumor with a unique tumor microenvironment (TME) that extends to the peritoneal cavity. The immunosuppressive nature of TME imposes the major challenge to develop effective treatment options for HGSOC. Interaction of immune cells in TME is an important factor. Hence, a better understanding of immune profile of TME may be required for exploring alternative treatment options. Immune profiling of peritoneal fluid (PF), tumor specimens, and blood were carried out using flowcytometry, ELISA, and Procartaplex immunoassay. The frequency of CD56BrightNK cells and expression of functional receptors were reduced in PF. Increased activating NKp46+CD56DimNK cells may indicate differential antitumor response in PF. Functional receptors on NK, NKT-like and T cells were reduced more drastically in tumor specimens. Soluble ligands MIC-B and PVR were reduced, whereas B7-H6 was increased in PF. Dissemination of tumor cells contributes to soluble ligands in PF. A differential cytokine profile was found in serum and PF as IL-2, IL-8, IL-15, IL-27, IFN-γ, and GM-CSF were elevated specifically in PF. In conclusion, the differential immune profile and correlation of soluble parameters and NK cell receptors with chemo response score may add knowledge to understand anti-tumor immune response to develop effective treatment modality.

Human papillomavirus infection: Is it associated with epithelial ovarian cancer?

PURPOSE: Human papillomavirus (HPV), the causative agent of cervical cancer, is associated with several other epithelial malignancies. Previous reports on HPV infection and its association with ovarian cancer are highly contradicting. Reports on HPV association with ovarian cancer in Indian women are also rare. Hence, the purpose of this study was to screen women with serous epithelial ovarian cancer for possible HPV infection. METHODS: Tumor samples, collected at the time of surgery from 88 women with serous epithelial ovarian cancer were screened using a specific and sensitive PCR. The PCR results were confirmed with Southern blotting using HPV genome-specific probes, both of high-risk HPV type 16 and 18 and low-risk HPV type 6 and 11. All the samples were again tested for another 14 high-risk HPV genotypes with a commercially available qRT-PCR. RESULTS: All the samples screened and confirmed by various tests did not show presence of either low-risk or high-risk HPV DNA, indicating the absence of HPV infections in these ovarian cancer tissues. CONCLUSIONS: The present study shows that HPV infection may not be associated with epithelial ovarian cancer. The result of the current investigation strongly supports the results of earlier research that, HPV is not associated with ovarian cancer.