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In Yangtze River Delta white goat, hypermethylation of CMTM3 leads to a decreased expression level in high quality brush hair. However, the regulation of CMTM3 expression and its function in hair follicle stem cells (HFSCs) remains largely unknown. In this study, we investigated the regulation of CMTM3 expression, function, and molecular mechanism in HFSCs. The re-expression of CMTM3 significantly suppressed the proliferation of HFSCs by inducing G1 cell cycle arrest and promoting apoptosis. Moreover, the downregulation of CMTM3 promoted HFSC proliferation. Treatment with sh_CMTM3 and incubation in a DHT culture medium had the most significant growth-promoting effect. It was hypothesized that transcriptome analysis using RNA sequencing (RNA-seq) in samples would enable the identification of unique protein-coding and non-coding genes that may help uncover the role of CMTM3. Multiple genes and pathways were involved in this process, including 168 common DEGs, such as CXCL8 and E-selectin, which is reportedly involved in multiple regulatory pathways. These results indicated that CMTM3 can function as HFSCs through the induction of a G1 cell cycle arrest and promoted apoptosis by mediating crosstalk between several pathways and transcription factors. Our data is available in the National Center for Biotechnology Information (NCBI) database with the accession number PRJNA657430. • A high expression level of CMTM3 inhibited the proliferation of hair follicle stem cells (HFSCs) and promoted cell apoptosis. Conversely, inhibiting the expression level of CMTM3 and adding androgens promoted the proliferation of HFSCs. • RNA-seq analysis showed that the differentially expressed genes (DEGs) related to CMTM3 were mainly connected to vasculature, the cardiovascular system, and the immune system. [ABSTRACT FROM AUTHOR]

Abstract: Micro-RNAs (miRNAs) have been found to be implicated in a very wide range of physiological processes. This study was aimed to investigate the regulation of miRNA-429 (miR-429) in gastric cancer cells on cell proliferation and apoptosis. Quantitative PCR was employed to detect the expressions of miR-429 after eukaryotic expression plasmid of miR-429 and its inhibitor were transiently transfected into poorly differentiated human gastric cancer cell line BGC823. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction as-says were used to examine proliferation ability. Apoptosis was analyzed by flow cytometry after transfection. The results showed that 48 h after transfection, overexpression of miR-429 reached maximum efficiency. Compared with mock transfection, miR-429 inhibited tumor cell proliferation significantly (P < 0.05) at 48 h and 72 h. of Overexpression of miR-429 promoted tumor cell apoptosis when compared with mock transfected cells (P < 0.05). On the contrary, miR-429 inhibitor promoted tumor cell proliferation and inhibited apoptosis when compared with controls (P < 0.05). Our results suggested that miRNA-429 may serve as a tumor suppressor during tumorigenesis of gastric cancer and may be a potential gastric cancer therapeutic target. [Copyright &y& Elsevier]

Resistomycin, a quinone-related natural antibiotic, has shown strong inhibitory activity against human hepatocellular carcinoma (HCC) in vitro. Here, we investigated the role of p38 MAPK in the pro-apoptotic and G2/M phase arrest action of HCC HepG2 cells upon treatment with resistomycin in vitro and in vivo. Our results showed that resistomycin dose- and time-dependently reduced the viability of HepG2 cells and also showed lower cytotoxicity in normal human kidney cells (293T) and hepatocyte cells (HL-7702). Resistomycin treatment induced apoptosis and cell cycle arrest in HepG2 cells, accompanied by changes in the expression of related proteins, including Bax, Cyclin B1, etc. Surprisingly, resistomycin-mediated apoptotic cell death and cell cycle arrest were impeded by SB203580 (an inhibitor of p38 catalytic activity), suggesting that p38 MAPK signaling may play an important role that impedes eventual cell death. In this connection, data in vitro and in vivo demonstrated that resistomycin increased the phosphorylation of p38 and MAPKAPK-2 in HepG2 cells. Furthermore, we provided evidence that p38 signaling is involved in resistomycin-induced p38 MAPK pathway effects in HCC, using computer docking models. Our study indicated that resistomycin activates the p38 MAPK signaling pathway by which the growth of HepG2 cells is suppressed for apoptosis and G2/M phase arrest in vitro and in vivo, and it is a promising therapeutic leading compound for drug development in HCC treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: In mammals, KISS-1 metastasis suppressor (KISS1) has emerged to stimulate the secretion of gonadotropin-releasing hormone (GnRH) to initiate the first estrus in the hypothalamus. However, KISS1 was recently demonstrated to be widely expressed in various ovarian compartments, including oocytes, granulosa cells (GCs) and theca cells. But the biological functionalities of KISS1 have not been explored in GCs. In this study, the overexpression plasmid of pcDNA3.1-KISS1 was built to explore the biological effects of KISS1 on the phosphoinositide 3-kinases (PI3K) signaling pathway, estrogen signaling pathway, cell apoptosis, cell cycle, and estradiol-17β (E2) secretion in porcine GCs. We found that overexpression of KISS1 could affect the PI3K signaling pathway, significantly decrease the apoptosis of GCs, and suppress GCs at G0/G1 phase of the cell cycle. Furthermore, overexpression of KISS1 could activate the estrogen synthesis signaling pathway and significantly increase the concentration of E2 in the supernatant and the mRNA expression levels of ESR1 and ESR2. These findings were highly accorded with the supposed role of KISS1 to promote the follicular development. This study would be of great interest for exploring the biological functionalities of KISS1 in regulating the maturation of follicles in mammals. Previous studies have strongly recommended that KISS-1 metastasis suppressor (KISS1) plays an essential gatekeeper of the initiation of reproductive maturation in mammals. However, KISS1 has been recently reported to highly express in ovarian granulosa cells (GCs). But the biological functionalities of KISS1 on cell apoptosis, cell cycle, and synthesis of estradiol-17β (E2) have not been explored in GCs. In this study, using porcine GCs as a cellular model, the overexpression plasmid of KISS1 was built to explore the biological effects of KISS1 on the PI3K signaling pathway, estrogen signaling pathway, cell apoptosis, cell cycle, and E2 secretion. We found that mRNA of KISS1 highly expressed in the ovary and significantly increased from immature to mature follicles in gilts. Overexpression of KISS1 could significantly increase the mRNA expression of PIK3CG, PIK3C1, and PDK1, and significantly decreased the mRNA levels of FOXO3, TSC2, and BAD of PI3K signaling pathway. Furthermore, results of the flow cytometry showed that overexpression of KISS1 significantly inhibited the apoptosis of GCs and decreased the percentage of GCs at G0/G1 phase of the cell cycle. Additionally, overexpression of KISS1 could increase the mRNA levels of Star, CYP17, 3B-HSD, 17B-HSD of estrogen synthesis signaling pathway, significantly increase the concentration of E2 in the supernatant of the cultured GCs, and up-regulate the mRNA expression levels of ESR1 and ESR2. These results suggested that KISS1 might suppress cell apoptosis through activating the PI3K signaling pathway and stimulate synthesis of E2 via boosting the estrogen synthesis signaling pathway. This study would be of great interests for exploring the biological functionalities of KISS1 in the folliculogenesis and sex steroid production of the ovaries in mammals. [ABSTRACT FROM AUTHOR]