Role of circular RNA/miRNA axes in the pathophysiology of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a disorder resulted from interactions between genetic and environmental factors. Based on the importance of epigenetic factors in the pathoetiology of PCOS, the current review focused on identification of circular RNAs (circRNAs) that are involved in PCOS through acting as molecular sponges for microRNAs (miRNAs). The literature search led to identification of circ_0043533/miR-1179, circ_0030018/miR-136, circ_FURIN/miR-423-5p, circ-FURIN/miR-195-5p, circ_0043532/miR-182, circ_RANBP9/miR-136-5p, circRHBG/miR-515-5p, circMTO1/miR-320b, circASPH/miR-375, circPSMC3/miR-296-3p, circLDLR/miR-1294, circPUM1/miR-760, and hsa_circ_0118530/miR-136 as molecular axes contributing to the pathogenesis of PCOS. To set the stage for future research on the role of the ceRNA network in PCOS, in-silico analyses were performed using miRWalk, miRNet, and miRDIP databases. miRWalk identified 80 genes regulated by 5 miRNAs, miRNet revealed 6449 circRNAs potentially controlling 11 miRNAs, and miRDIP identified 11 miRNAs associated with 35 human pathways. These targets can be used in the treatment options, design of personalized medicine and prediction of prognosis of PCOS.

Impact of miRNAs in the pathoetiology of recurrent implantation failure.

Recurrent implantation failure (RIF) is a condition with a multifactorial basis. Recent research has focused on the role of genetic factors in the pathophysiology of RIF. Of particular note, miRNAs have been found to contribute to the pathogenesis of RIF. Several miRNA polymorphisms have been investigated in this context. Moreover, dysregulation of expression of a number of miRNAs, including miR-374a-5p, miR-145-5p, miR-30b-5p, miR-196b-5p, miR-22, miR-181 and miR-145 has been found in RIF. This review concentrates on the role of miRNAs in RIF to help in identification of the molecular basis for this condition and design of more effective methods for management of RIF, especially in a personalized manner that relies on the expression profiles of miRNAs in the peripheral blood or endometrium.

Impacts of non-coding RNAs in the pathogenesis of varicocele.

Two classes of non-coding RNAs, namely lncRNAs and miRNAs have been reported to be involved in the pathogenesis of varicocele. MIR210HG, MLLT4-AS1, gadd7, and SLC7A11-AS1 are among lncRNAs whose expression has been changed in patients with varicocele in association with the sperm quality. Animal studies have also suggested contribution of NONRATG001060, NONRATG002949, NONRATG013271, NONRATG027523 and NONRATG023747 lncRNAs in this pathology. Meanwhile, expression of some miRNAs, such as miR-210-3p, miR-21, miR-34a, miR-122a, miR-181a, miR-34c and miR-192a has been altered in this condition. Some of these transcripts have the potential to predict the sperm quality. We summarize the impacts of lncRNAs and miRNAs in the pathogenesis of varicocele.

A review on the role of KCNQ1OT1 lncRNA in human disorders.

KCNQ1OT1 is an lncRNA located within KCNQ1 gene on chromosome 11p15.5. This lncRNAs participates in the pathogenesis of a diversity of cancers as well as non-cancerous conditions. In most types of cancers, KCNQ1OT1 is regarded as an oncogene. In a wide array of cancers, high level of KCNQ1OT1 is associated with lower overall survival time. This lncRNA has been found to adsorb a variety of miRNAs, namely miR-15a, miR-211-5p, hsa-miR-107, miR-145, miR-34a, miR-204-5p, miR-129-5p, miR-372-3p, miR-491-5p, miR-153, miR-185-5p, miR-124-3p, miR-211-5p, miR-149, miR-148a-3p, miR-140-5p, miR-125b-5p, miR-9, miR-329-3p, miR-760, miR-296-5p, miR-3666 and miR-129-5p, thus regulating the downstream targets of these miRNAs. In this manuscript, our attention is on this lncRNA and its biomolecular roles in human cancers and other disorders. KCNQ1OT1 plays significant roles in the tumorigenesis and may function as a prospective target for cancer therapy.

Emerging role of lncRNAs in the etiology of recurrent implantation failure.

Recurrent implantation failure (RIF) is a complex clinical entity with several molecular pathways contributing to its pathogenesis. Long non-coding RNAs (lncRNAs) have recently been found to affect the normal implantation, thus aberrant expression of these transcripts is involved in RIF. Altered expression of HOXA11-AS, NONHSAT193031.1, NONHSAT053761.2, NONHSAT083203.2, LUCAT1, PART1, TUNAR, LINC02190, lncSAMD11-1:1 and H19 has been reported in this condition. Moreover, polymorphisms within some lncRNAs have been shown to be associated with miscarriage/RIF. The current review article summarizes the recent data about the role of lncRNAs in RIF. This information would pave the way for identification of the molecular events in this context.

MicroRNA-125a-3p, -4530, and -92a as a Potential Circulating MicroRNA Panel for Noninvasive Pancreatic Cancer Diagnosis.

MicroRNA (miRNA) expression dysregulations in pancreatic ductal adenocarcinoma (PDAC) have been studied widely for their diagnostic and prognostic utility. By the use of bioinformatics-based methods, in our previous study, we identified some potential miRNA panels for diagnosis of pancreatic cancer patients from noncancerous controls (the screening stage). In this report, we used 142 plasma samples from people with and without pancreatic cancer (PC) to conduct RT-qPCR differential expression analysis to assess the strength of the first previously proposed diagnostic panel (consisting of miR-125a-3p, miR-4530, and miR-92a-2-5p). As the result, we identified significant upregulation for all the three considered miRNAs in the serum of PC patients. After that, a three-miRNA panel in serum was developed. The area under the receiver operating characteristic curves (AUC) for the panel were 0.850, 0.910, and 0.86, respectively, indicating that it had a higher diagnostic value than individual miRNAs. Therefore, we detected a promising three-miRNA panel in the plasma for noninvasive PC diagnosis (miR-125a-3p, miR-4530, and miR-92a-2-5p).

Evaluation of potential of miR-8073 and miR-642 as diagnostic markers in pancreatic cancer.

BACKGROUND: Pancreatic cancer is a cancer with an insidious course. Since disease is often diagnosed at advanced stages, clinical outcome is impaired. Thus identification of biomarkers for this malignancy has importance in enhancement of patients' survival. METHODS AND RESULTS: In the current study, we assessed expression levels of miR-8073 and miR-642 in the circulation of 50 patients with pancreatic cancer and 50 controls. Plasma levels of miR-8073 and miR-642 were significantly higher in patients with pancreatic cancer compared with controls (P value < 0.0001 and P value = 0.0068, respectively). Plasma levels of miR-642 were inversely correlated with albumin levels (R=-0.28, P value = 0.049), WBC count (R=-0.35, P value = 0.01), as well as CRP level (R=-0.30, P value = 0.035). On the other hand, levels of this miRNA were positively correlated with lipase level (R = 0.29, P value = 0.042). Levels of miR-8073 were not correlated with any of the available parameters. Plasma levels of miR-8073 could separate patients with pancreatic cancer from controls with AUC, sensitivity and specificity values of 0.82, 0.77 and 0.78, respectively. miR-642 could differentiate these two groups with AUC, sensitivity and specificity values of 0.63, 0.58 and 0.78, respectively. Combination of these two parameters resulted in AUC, sensitivity and specificity values of 0.79, 0.77 and 0.78, respectively. CONCLUSIONS: Taken together, these two miRNAs are suggested as possible blood markers for pancreatic cancer.

Expression analysis of IFNAR1 and TYK2 transcripts in COVID-19 patients.

As a member of JAK family of non-receptor tyrosine kinases, TYK2 has a crucial role in regulation of immune responses. This protein has a crucial role in constant expression of IFNAR1 on surface of cells and initiation of type I IFN signaling. In the current study, we measured expression of IFNAR1 and TYK2 levels in venous blood samples of COVID-19 patients and matched controls. TYK2 was significantly down-regulated in male patients compared with male controls (RME = 0.34, P value = 0.03). Though, levels of TYK2 were not different between female cases and female controls, or between ICU-admitted and non-ICU-admitted cases. Expression of IFNAR1 was not different either between COVID-19 cases and controls or between patients required ICU admission and non-ICU-admitted cases. However, none of these transcripts can properly diffrentiate COVID-19 cases from controls or separate patients based on disease severity. The current study proposes down-regulation of TYK2 as a molecular mechanism for incapacity of SARS-CoV-2 in induction of a competent IFN response.

Down-regulation of MEG3, PANDA and CASC2 as p53-related lncRNAs in breast cancer.

TP53 encodes a major tumor suppressor protein which blocks carcinogenesis process in a variety of tissues including breast tissue. Expression and function of this gene is regulated by a number of long non-coding RNAs (lncRNAs) among them are PANDA, MEG3 and CASC2. We measured expression of TP53 and these transcripts in a cohort of Iranian breast cancer patients. Expression levels of TP53, MEG3, CASC2 and PANDA were significantly lower in tumoral samples compared with non-tumoral samples (Posterior mean differences = -4.26, -1.66, -5.98 and -3.13, respectively; P values < 0.0001). Expression of CASC2 was higher in Her2 1+ cases compared with Her2 negative cases (Beta = 1.85, P value = 0.037). Expression levels of MEG3 and TP53 were lower in grade 2 samples compared with grade 1 (Beta = -1.86, P value = 0.006 and Beta = -2.24, P value = 0.003, respectively). There was no other significant association between expression of genes and clinical variables. CASC2 had the best performance among these genes with area under curve value of 0.78 and sensitivity and specificity values of 56.33% and 88.73%, respectively (P value < 0.0001). The current investigation supports the role of TP53-related lncRNAs in the pathogenesis of breast cancer.

LncRNAs: Novel Biomarkers for Pancreatic Cancer.

Pancreatic cancer is one of the most deadly neoplasms and the seventh major cause of cancer-related deaths among both males and females. This cancer has a poor prognosis due to the lack of appropriate methods for early detection of cancer. Long non-coding RNAs (lncRNAs) have been recently found to influence the progression and initiation of pancreatic cancer. MACC1-AS1, LINC00976, LINC00462, LINC01559, HOXA-AS2, LINC00152, TP73-AS1, XIST, SNHG12, LUCAT1, and UCA1 are among the oncogenic lncRNAs in pancreatic cancer. On the other hand, LINC01111, LINC01963, DGCR5, MEG3, GAS5, and LINC00261 are among tumor suppressor lncRNAs in this tissue. In the current review, we summarize the roles of these two classes of lncRNAs in pancreatic cancer and discuss their potential as attractive diagnostic and prognostic biomarkers for pancreatic cancer. We also identified that the low expression of MEG3, LINC01963, and LINC00261 and the high expression of MACC1-AS1, LINC00462, LINC01559, and UCA1 were significantly correlated with worse survival in pancreatic cancer patients. Further research on these lncRNAs will provide new clues that could potentially improve the early diagnosis, prognostic prediction, and personalized treatments of patients with pancreatic cancer.

Emerging roles of miRNAs in the development of pancreatic cancer.

Pancreatic cancer is a fatal cancer which is expected to exceed breast cancer as the third foremost source of cancer mortality by 2025. This cancer has been associated with several somatic genetic aberrations including mutations in the KRAS, CDKN2A/p16, TP53, and SMAD4. In addition, epigenetic alterations have been shown to affect development of this cancer. miRNAs are among the mostly appreciated epigenetic factors in this regard. Several oncomiRs such as miR-212, miR 506, miR-196b, miR-221-3p, miR-301a-3p, miR-23a and miR-29a have been found to promote proliferation of pancreatic cancer cells and block apoptotic pathways in these cells. On the other hand, miR-451a, miR-506, miR-142, miR-216b, miR-519d-3p, miR-1181, miR-340, miR-143-3p, miR-203a-3p, miR-455, miR-15a, miR-135a and miR-202 are among tumor suppressor miRNAs that modulate proliferation and cell cycle transition in these cells. In the current paper, we will discuss the role of oncomiRs and tumor suppressor miRNAs in the evolution of pancreatic cancer. Moreover, we will summarize the application of miRNAs as diagnostic and prognostic markers in pancreatic cancer. These studies have shown the ability of miRNAs to be served as non-invasive markers for pancreatic cancer.