The Role of ncRNAs in the Immune Dysregulation of Preeclampsia.

The main complications causing practically 75% of all maternal deaths are severe bleeding, infections, and high blood pressure during pregnancy (preeclampsia (PE) and eclampsia). The usefulness of ncRNAs as clinical biomarkers has been explored in an extensive range of human diseases including pregnancy-related diseases such as PE. Immunological dysregulation show that the Th1/17:Th2/Treg ratio is "central and causal" to PE. However, there is evidence of the involvement of placenta-expressed miRNAs and lncRNAs in the immunological regulation of crucial processes of placenta development and function during pregnancy. Abnormal expression of these molecules is related to immune physiopathological processes that occur in PE. Therefore, this work aims to describe the importance of miRNAs and lncRNAs in immune dysregulation in PE. Interestingly, multiple ncRNAS are involved in the immune dysregulation of PE participating in type 1 immune response regulation, immune microenvironment regulation in placenta promoting inflammatory factors, trophoblast cell invasion in women with Early-Onset PE (EOPE), placental development, and angiogenesis, promotion of population of M1 and M2, proliferation, invasion, and migration of placental trophoblast cells, and promotion of invasion and autophagy through vias such as PI3K/AKT/mTOR, VEGF/VEGFR1, and TLR9/STAT3.

The Two Faces of Immune-Related lncRNAs in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a group of cancers originating from the mucosal epithelium in the oral cavity, larynx, oropharynx, nasopharynx, and hypopharynx. Molecular factors can be key in the diagnosis, prognosis, and treatment of HNSCC patients. Long non-coding RNAs (lncRNAs) are molecular regulators composed of 200 to 100,000 nucleotides that act on the modulation of genes that activate signaling pathways associated with oncogenic processes such as proliferation, migration, invasion, and metastasis in tumor cells. However, up until now, few studies have discussed the participation of lncRNAs in modeling the tumor microenvironment (TME) to generate a protumor or antitumor environment. Nevertheless, some immune-related lncRNAs have clinical relevance, since AL139158.2, AL031985.3, AC104794.2, AC099343.3, AL357519.1, SBDSP1, AS1AC108010.1, and TM4SF19-AS1 have been associated with overall survival (OS). MANCR is also related to poor OS and disease-specific survival. MiR31HG, TM4SF19-AS1, and LINC01123 are associated with poor prognosis. Meanwhile, LINC02195 and TRG-AS1 overexpression is associated with favorable prognosis. Moreover, ANRIL lncRNA induces resistance to cisplatin by inhibiting apoptosis. A superior understanding of the molecular mechanisms of lncRNAs that modify the characteristics of TME could contribute to increasing the efficacy of immunotherapy.

Emerging role of lncRNAs in drug resistance mechanisms in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) originates in the squamous cell lining the mucosal surfaces of the head and neck region, including the oral cavity, nasopharynx, tonsils, oropharynx, larynx, and hypopharynx. The heterogeneity, anatomical, and functional characteristics of the patient make the HNSCC a complex and difficult-to-treat disease, leading to a poor survival rate and a decreased quality of life due to the loss of important physiologic functions and aggressive surgical injury. Alteration of driver-oncogenic and tumor-suppressing lncRNAs has recently been recently in HNSCC to obtain possible biomarkers for diagnostic, prognostic, and therapeutic approaches. This review provides current knowledge about the implication of lncRNAs in drug resistance mechanisms in HNSCC. Chemotherapy resistance is a major therapeutic challenge in HNSCC in which lncRNAs are implicated. Lately, it has been shown that lncRNAs involved in autophagy induced by chemotherapy and epithelial-mesenchymal transition (EMT) can act as mechanisms of resistance to anticancer drugs. Conversely, lncRNAs involved in mesenchymal-epithelial transition (MET) are related to chemosensitivity and inhibition of invasiveness of drug-resistant cells. In this regard, long non-coding RNAs (lncRNAs) play a pivotal role in both processes and are important for cancer detection, progression, diagnosis, therapy response, and prognostic values. As the involvement of more lncRNAs is elucidated in chemoresistance mechanisms, an improvement in diagnostic and prognostic tools could promote an advance in targeted and specific therapies in precision oncology.

More Evidence of the Link of Interleukin-6 and Interleukin-10 with Critical COVID-19: A Report in Mexican Patients.

BACKGROUND: According to the World Health Organization, Mexico presents one of the highest mortality rates due to coronavirus disease 2019 (COVID-19). The "cytokine storm" phenomenon has been proposed as a pathological hallmark of severe COVID-19. OBJECTIVE: To determine the association of serum cytokine levels with COVID-19 severity. METHODS: We studied the cytokines IL-2, IL-4, IL-6, IL-10, TNF-α, and the IFN-γ serum levels through flow cytometry in 56 COVID-19 patients (24 critical and 32 non-critical) from Northwest Mexico. RESULTS: We observed a significant increase in the IL-6 and the IL-10 levels in the sera of critical patients. These cytokines were also associated with mechanical ventilation necessity and death, IL-6 showing AUC values above 0.7 for both variables; and correlated with Na+, creatinine, and platelet levels. On the other hand, no association was found between IL-2, IL-4, TNF-α, and IFN-γ with tested variables. CONCLUSION: Our results corroborate previous observations regarding IL-6 and IL-10 involvement in the severity of COVID-19.

Cell Survival Is Regulated via SOX9/BCL2L1 Axis in HCT-116 Colorectal Cancer Cell Line.

Colorectal cancer (CRC) is one of the most frequent types of malignancies and one of the major causes of cancer-related death worldwide. Sex-determining region Y (SRY)-box 9 protein (SOX9) is a member of the SOX family of transcription factors which are involved in the regulation of differentiation and development. Recently, several reports suggest an important role of SOX9 in tumorigenesis since its overexpression correlates with tumor progression and poor outcome in several types of cancer; however, its role in CRC is not clear until now. Therefore, in this work, we searched for novel SOX9-regulated genes involved in cell survival of CRC. We silenced SOX9 in the poorly differentiated HCT-116 cell line, using a specific siRNA, to identify differential expressed genes by DNA microarrays and analyzed the role or candidate genes in apoptosis and autophagy. Transcriptome analysis showed that diverse cellular pathways, associated with CRC carcinogenesis such as Wnt/ß-catenin, MAPK, TGF-ß, and mTOR, were modulated after SOX9 silencing. Interestingly, we found that SOX9 silencing promotes downregulation of BCL2L1 and overexpression of CASP3, proteins related to apoptosis, which was further confirmed in SW-480, a moderated-differentiated cell line, but not in HT-29, well-differentiated cell line. Moreover, inhibition of BCL2L1 by ABT-737 (BH3 mimetic) in SOX9-silenced HCT-116 cells resulted in an increased apoptosis percentage. However, downregulation of BCL2L1 was not enough to induce autophagy. This is the first report, suggesting that cell survival in poorly and moderated-differentiated CRC cells lines is regulated by SOX9/BCL2L1 axis, but not in well-differentiated cell lines.