Vomeronasal Receptors Associated with Circulating Estrogen Processing Chemosensory Cues in Semi-Aquatic Mammals.

In numerous animals, one essential chemosensory organ that detects chemical signals is the vomeronasal organ (VNO), which is involved in species-specific behaviors, including social and sexual behaviors. The purpose of this study is to investigate the mechanism underlying the processing of chemosensory cues in semi-aquatic mammals using muskrats as the animal model. Muskrat (Ondatra zibethicus) has a sensitive VNO system that activates seasonal breeding behaviors through receiving specific substances, including pheromones and hormones. Vomeronasal organ receptor type 1 (V1R) and type 2 (V2R) and estrogen receptor α and ß (ERα and ERß) were found in sensory epithelial cells, non-sensory epithelial cells and lamina propria cells of the female muskrats' VNO. V2R and ERα mRNA levels in the VNO during the breeding period declined sharply, in comparison to those during the non-breeding period, while V1R and ERß mRNA levels were detected reversely. Additionally, transcriptomic study in the VNO identified that differently expressed genes might be related to estrogen signal and metabolic pathways. These findings suggested that the seasonal structural and functional changes in the VNO of female muskrats with different reproductive status and estrogen was regulated through binding to ERα and ERß in the female muskrats' VNO.

Lung squamous cell carcinoma presenting as rare clustered cystic lesions: A case report and review of literature.

BACKGROUND: Lung cancer is the leading cause of cancer-related death. Early diagnosis is critical to improving a patient's chance of survival. However, lung cancer associated with cystic airspaces is often misdiagnosed or underdiagnosed due to the absence of clinical symptoms, poor imaging specificity, and high risk of biopsy-related complications. CASE SUMMARY: We report an unusual case of cancer in a 55-year-old man, in which the lesion evolved from a small solitary thin-walled cyst to lung squamous cell carcinoma (SCC) with metastases in both lungs. The SCC manifested as rare clustered cystic lesions, detected on chest computed tomography. There were air-fluid levels, compartments, and bronchial arteries in the cystic lesions. Additionally, there was no clear extrathoracic metastasis. After chemotherapy, the patient achieved a partial response, type I respiratory failure was relieved, and the lung lesions became a clustered thin-walled cyst. CONCLUSION: Pulmonary cystic lesions require regular imaging follow-up. Lung SCC should be a diagnostic consideration in cases of thin-walled cysts as well as multiple clustered cystic lesions.

Long non-coding RNA LINC01194 promotes the inflammatory response and apoptosis of lipopolysaccharide-treated MLE-12 cells through the miR-203a-3p/MIP-2 axis.

Acute lung injury (ALI) induced by bacteria lipopolysaccharide (LPS) is characterized by the upregulation of the apoptosis rate of tissue cells and aggravation of inflammatory response. Although many studies have focused on the pathogenesis of this disease, its mechanism remains unknown. This study examined the regulatory role of long non-coding RNA (lncRNA) LINC01194 in the progression of ALI through various bioinformatics analyses and experimental work, including ELISA assay, dual-luciferase reporter assay, biotinylated RNA pull-down assay, and Western blot analysis. The result showed that the LINC01194 was overexpressed in the ALI-induced mice model. We observed a significant upregulation of LINC01194 in LPS-treated mouse lung epithelial type II cells (MLE-12 cells) after 24 h of induction. Bioinformatics analysis, ELISA assay, quantitative reverse transcription polymerase chain reaction analysis, biotinylated RNA pull-down assay, apoptosis test, and Western blot analysis demonstrated that the LINC01194 could act as a microRNA (miR) miR-203a-3p sponge to activate the inflammatory response in LPS-induced ALI model through post-transcriptional upregulation of macrophage inflammatory protein (MIP-2). We showed that LINC01194 regulates the inflammatory response and apoptosis of LPS-induced mice and MLE-12 cells via the miR-203a-3p/MIP-2 axis. LINC01194 could be a potential biomarker for early diagnosis and the treatment of ALI.

Suppression of HELLS by miR-451a represses mTOR pathway to hinder aggressiveness of SCLC.

BACKGROUND: Uncovering molecular pathogenesis and mechanisms of small cell lung cancer (SCLC) will contribute to SCLC therapy. Multiple studies demonstrated that miR-451a acts as an anti-tumor miRNA in non-small cell lung cancer. However, the mechanism of miR-451a in SCLC was ambiguous. OBJECTIVE: We aimed to explore the function of miR-451a in SCLC and decipher the underlying mechanisms. METHODS: TargetScan and dual-luciferase reporter assays were used to analyze the target genes of miR-451a. Cell counting kit-8 and colony formation assays were performed to assess the roles of miR-451a on cell growth. Gene set enrichment analysis (GSEA) was utilized to enrich biological pathways. Western blot was used to measure protein expression. RESULTS: MiR-451a expression was reduced dramatically in SCLC tissues and cell lines (NCI-H1688 and NCI-H446). Helicase, Lymphoid Specific (HELLS) was proved to be a target gene of miR-451a. In addition, cell proliferation assays in SCLC cells transfected with miR-451a mimic and/or HELLS revealed that miR-451a inhibited cell proliferation via targeting HELLS. Moreover, the roles of miR-451a/HELLS in expression of key proteins in mTOR and apoptosis signaling pathways suggested that miR-451a inactivated mTOR and activated apoptosis signaling pathway via directly silencing HELLS. CONCLUSIONS: Our study indicated that miR-451a hinders SCLC cell proliferation in vitro through regulating mTOR and apoptosis signaling pathways via silencing HELLS, suggesting that miR-451a could be a promising tumor suppressor in SCLC. And there is a potential for miR-451a to be a drug target and biomarker for SCLC.

MiR-133a acts as a tumor suppressor in lung cancer progression by regulating the LASP1 and TGF-ß/Smad3 signaling pathway.

BACKGROUND: MiR-133a has been confirmed to be involved in the development of multiple cancers including non-small cell lung cancer (NSCLC). However, the precise molecular mechanism has not yet been fully elucidated. The purpose of this study was to investigate the functional role and underlying mechanism of miR-133a in the progression of NSCLC. METHODS: Quantitative real-time PCR (qRT-PCR) was performed to measure miR-133a and LASP1 expression in NSCLC tissues and cells. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to detect cell viability. The protein levels were measured by western blot. The tumor growth was measured by xenograft tumor formation assay. RESULTS: miR-133a was significantly decreased while LASP1 was increased in NSCLC tissues and cells compared with control groups. Moreover, overexpression of miR-133a suppressed cell viability, whereas miR-133a knockdown enhanced the viability of A549 cells. More importantly, LASP1 was verified as a direct target of miR-133a. Moreover, overexpression of miR-133a inhibited the epithelial-mesenchymal transition (EMT) and TGF-ß/Smad3 pathways by regulating LASP1 in vitro. In addition, miR-133a mimic suppressed tumor growth by modulating the TGF-ß/Smad3 pathway in vivo. CONCLUSIONS: In conclusion, miR-133a acted as a tumor suppressor in lung cancer progression by regulating the LASP1 and TGF-ß/Smad3 signaling pathway.

Seasonal expressions of prostaglandin E synthases and receptors in the prostate of the wild ground squirrel (Spermophilus dauricus).

The prostate gland is a male accessory reproductive gland, whose vitality and function are under tight regulation of different hormones. Prostaglandins E2 (PGE2) is one of the major products generated by the actions of cyclooxygenases (COX) and prostaglandin E synthase (PTGES) on arachidonic acid, and is involved in a number of physiological and pathological processes. In this study, we investigated the seasonal immunolocalizations and expressions of COX-1, COX-2 and PTGES, as well as PGE2 receptors (PTGERs) subtypes 1-4 (EP1, EP2, EP3, EP4) in the prostate of the wild ground squirrel. Histological examination observed enlarged prostatic lumens in the breeding season and significantly shrunken lumens in the nonbreeding season. COX-1, COX-2, PTGES and PTGERs were mainly localized in epithelial and stromal cells in the breeding and nonbreeding seasons. The mRNA expression levels of Cox-1, Cox-2, Ptges, Ptger2 (encoding EP2) and Ptger4 (encoding EP4) were higher in the prostate of the breeding season than in the nonbreeding season. The relative mRNA levels of Cox-1, Cox-2, Ptges, Ptger2 and Ptger4 were positively correlated with prostatic weights. In addition, both the prostatic and plasma concentrations of PGE2 were significantly higher in the breeding season compared to the nonbreeding season. These results suggested that PGE2 synthesis and signaling might play an important autocrine or paracrine role in the regulation of seasonal changes in the prostatic function of the wild ground squirrel.

MicroRNA-133a inhibits the proliferation of non-small cell lung cancer by targeting YES1.

Previous studies have reported that microRNA-133a (miR-133a) is involved in the pathogenesis of human cancers. This study investigated the effect of miR-133a on cell proliferation in non-small cell lung cancer (NSCLC). The expression of miR-133a and YES proto-oncogene 1 (YES1) was detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay. The CCK-8 assay was used to measure cell proliferation. The relationship between miR-133a and YES1 was confirmed by dual luciferase assay. Downregulation of miR-133a was identified in NSCLC and correlated with poor prognosis in NSCLC patients. Moreover, the overexpression of miR-133a inhibited proliferation of NSCLC cells. YES1 was also confirmed as a direct target of miR-133a. Downregulation of YES1 was found to inhibit cell proliferation in NSCLC. By contrast, the upregulation of YES1 abolished the inhibitory effect of miR-133a on cell proliferation in NSCLC. miR-133a inhibited cell proliferation in NSCLC by targeting YES1, indicating that miR-133a can be used as an indicator of prognosis in NSCLC patients.

Endostar regulates EMT, migration and invasion of lung cancer cells through the HGF-Met pathway.

AIM: Though Endostar (ES) could inhibit tumor growth by inhibiting tumor angiogenesis, other possible mechanisms have been less reported. This study aims to investigate the role of ES in the treatment of lung cancer from the perspective of macrophage-mediated epithelial mesenchymal transformation (EMT). METHODS: THP1 cells were induced to polarized macrophages (MΦ). A549 and H1795 cells were separately treated with MΦ conditioned medium, ES (12.5 µg/ml) and HGF (5 ng/ml) for 24 h at 37 °C. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression levels of CCL17, CD163, hepatocyte growth factor (HGF), Epidermal Growth Factor (EGF), transforming growth factor (TGF)-ß1 and interleukin (IL)-6. Western blot was carried out to detect the p-MET, MET and EMT-related proteins (E-cadherin, N-cadherin, Snail and vimentin). Fibroblast-like A549 and H1975 cells were observed by a microscope. Cell invasion and migration were observed and analyzed by transwell and scratch assays. RESULTS: The expression levels of CCL17 and CD163 were significant higher in MΦ. ES significantly inhibited the expression of HGF in MΦ. Moreover, ES could restore the abnormal expressions of EMT-related proteins and inhibit MΦ-induced and HGF-induced fibroblast-like lung cancer cells. Furthermore, ES suppressed the MΦ-induced and HGF-induced migration and invasion of lung cancer cells. ES was also found to down-regulate HGF-Met signaling in HGF-treated lung cancer cells. CONCLUSION: ES suppresses lung cancer progression by down-regulating HGF-Met signaling, revealing the possible mechanism of ES in the process of treating lung cancer patients.