NLRC5 promotes tumorigenesis by regulating the PI3K/AKT signaling pathway in cervical cancer.

Cervical cancer (CC) is the fourth most common cancer among women worldwide. NLR Family CARD Domain Containing 5 (NLRC5) plays an important role in tumorigenesis. However, its effect and mechanism in CC remains unclear. In this study, we aimed to investigate the function of NLRC5 in CC. NLRC5 was found to be down-regulated in CC tissues compared with normal cervical tissues. However, patients with higher NLRC5 expression had better prognosis, patients with higher age, HPV infection, lymph node metastasis, recurrence and histological grade had worse prognosis. Univariate and multivariate analyses showed NLRC5 to be a potential prognostic indicator for CC. Pearson correlation analysis showed that NLRC5 might exert its function in CC through autophagy related proteins, especially LC3. In vitro experiments demonstrated that NLRC5 inhibited LC3 levels and promoted the proliferation, migration, and invasion of CC cells by activating the PI3K/AKT signaling pathway. Treatment with LY294002 reversed the above phenotype. Taken together, our finding suggested that NLRC5 would participate in cervical tumorigenesis and progression by regulating PI3K/AKT signaling pathway. In addition, NLRC5 and LC3 combined as possible predictors in CC.

Geographic population genetic structure and diversity of Sophora moorcroftiana based on genotyping-by-sequencing (GBS).

Sophora moorcroftiana is a perennial leguminous low shrub endemic to the Yarlung Zangbo River basin in Tibet with irreplaceable economic and ecological value. To determine the drivers of evolution in this species, 225 individuals belonging to 15 populations from different geographic locations were sampled, and population genetics was studied using high-throughput genotyping-by-sequencing (GBS). Based on genetic diversity analysis, phylogenetic analysis, principal component analysis, and structure analysis, 15 natural populations were clustered into the following five subgroups: subgroup I (Shigatse subgroup) was located in the upper reaches of the Yarlung Zangbo River with a relatively high level of population genetic variation (means for PIC, Shannon and PI were 0.173, 0.326 and 0.0000305, respectively), and gene flow within the subgroup was also high (mean value for Nm was 4.67). Subgroup II (including Pop 7 and Pop 8; means for PIC, Shannon and PI were 0.182, 0.345 and 0.0000321, respectively), located in the middle reaches of the Yarlung Zangbo River had relatively high levels of gene flow with the populations distributed in the upper and lower reaches. The Nm between subgroup II with subgroups I and III was 3.271 and 2.894, respectively. Considering all the genetic diversity indices Pop 8 had relatively high genetic diversity. Subgroup III (the remaining mixed subgroup of Lhasa and Shannan) was located in the middle reaches of the Yarlung Zangbo River and the means for PIC, Shannon and PI were 0.172, 0.324 and 0.0000303, respectively. Subgroup IV (Nyingchi subgroup), located in the lower reaches of the Yarlung Zangbo River basin, showed a further genetic distance from the other subgroups and the means for PIC, Shannon and PI were 0.147, 0.277 and 0.0000263, respectively. Subgroup V (Nyingchi Gongbu Jiangda subgroup), located in the upper reaches of the Niyang River, had the lowest level of genetic variation (means for PIC, Shannon and PI were 0.106, 0.198 and 0.0000187, respectively) and gene flow with other populations (mean value for Nm was 0.42). According to the comprehensive analysis, the S. moorcroftiana populations generally expanded from upstream to downstream and displayed a high level of genetic differentiation in the populations in the upper and lower reaches. There were high levels of gene exchange between the central populations with upstream and downstream populations, and wind-induced seed dispersal was an important factor in the formation of this gene exchange mode.

Circular RNAs: Novel biomarkers for cervical, ovarian and endometrial cancer (Review).

Cervical, ovarian and endometrial cancer are the three most common types of malignant tumor and the leading causes of cancer­associated death in women. Tumor debulking surgery followed by platinum and paclitaxel chemotherapy is the current treatment regime of choice. However, as a result of late diagnosis and chemoresistance, the survival rates of patients with advanced gynecological cancers remains unsatisfactory. Circular RNAs (circRNAs) are stable noncoding RNAs that are present in a wide variety of tissue and cell types. With the enhancement of RNA sequencing methods, increasing numbers of circRNAs have been identified, and their functions are gradually being revealed. In recent years, circRNAs have received increasing attention for their regulatory roles in cervical, ovarian and endometrial cancer. The aim of the present review was to summarize the possible mechanisms of recently identified circRNAs; we hypothesize that a novel diagnostic and therapeutic biomarker may be identified to prolong the survival time of patients with gynecological malignancies.

NLRC5 Inhibits Inflammation of Secretory Phase Ectopic Endometrial Stromal Cells by Up-Regulating Autophagy in Ovarian Endometriosis.

Nod-like receptor (NLR) family caspase activation and recruitment domain containing 5 (NLRC5) is a newly identified sub-class of the NLR family. It regulates inflammation and has a key function in innate and adaptive immunologic reactions. Autophagy has been reported to be crucially linked to the pathogenesis of endometriosis. Our recent study identify there is a negative correlation between NLRC5 and autophagy in endometriosis, indicating that NLRC5 and autophagy together act as promising predictors in endometriosis patients. However, the mechanism associating NLRC5 and autophagy in endometriosis is still not completely understood. We hypothesize that autophagy could be involved in NLRC5-mediated inflammation in endometriosis. In order to validate the assumption, we evaluate the effects of NLRC5 and autophagy in the inflammation of ectopic endometrial stromal cells (EESCs) of ovarian endometriosis patients, to specifically determine whether autophagy is involved in NLRC5-mediated inflammation in EESCs. Our results show that over-expression of NLRC5 results in the up-regulation of autophagy in EESCs and inhibition of NLRC5 restricts the level of autophagy in EESCs. Furthermore, over-expression of NLRC5 and promotion of autophagy inhibit interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expressions, whereas inhibition of NLRC5 and autophagy up-regulate IL-6 and TNF-α expressions in EESCs. Additionally, promotion of autophagy contributes to the NLRC5-mediated inhibition of IL-6 and TNF-α expressions in EESCs; inhibition of autophagy restricts NLRC5-mediated inhibition of IL-6 and TNF-α expressions in EESCs. Our results suggest that over-expression of NLRC5 promotes autophagy, thereby inhibiting inflammation in ovarian endometriosis.

Potential relationship between Sirt3 and autophagy in ovarian cancer.

Sirtuin 3 (Sirt3) is an important member of the sirtuin protein family. It is a deacetylase that was previously reported to modulate the level of reactive oxygen species (ROS) production and limit the extent of oxidative damage in cellular components. As an important member of the class III type of histone deacetylases, Sirt3 has also been documented to mediate nuclear gene expression, metabolic control, neuroprotection, cell cycle and proliferation. In ovarian cancer (OC), Sirt3 has been reported to regulate cellular metabolism, apoptosis and autophagy. Sirt3 can regulate autophagy through a variety of different molecular signaling pathways, including the p62, 5'AMP-activated protein kinase and mitochondrial ROS-superoxide dismutase pathways. However, autophagy downstream of Sirt3 and its association with OC remains poorly understood. In the present review, the known characteristics of Sirt3 and autophagy were outlined, and their potential functional roles were discussed. Following a comprehensive analysis of the current literature, Sirt3 and autophagy may either serve positive or negative roles in the regulation of OC. Therefore, it is important to identify the appropriate expression level of Sirt3 to control the activation of autophagy in OC cells. This strategy may prove to be a novel therapeutic method to reduce the mortality of patients with OC. Finally, potential research directions into the association between Sirt3 and other signaling pathways were provided.