Small cell lung cancer (SCLC) is highly aggressive and prone to hypervascular metastases. Recently, we found profilin 2 (PFN2) expression in SCLC but not in normal tissues. Furthermore, PFN2 expression had been shown to promote angiogenesis through exosomes. However, it remains unclear whether PFN2 contributes to the progression and metastasis of SCLC through angiogenesis. We report here that overexpression (OE) of PFN2 increased, whereas its knockdown (KD) decreased the proliferation, migration, and invasion of SCLC cell H446. The exosomes from OE-H446 (SCLC-OE-exo) exhibited similar effects on H446 properties. Culturing of endothelial cells (ECs) in SCLC-OE conditioned medium (CM) or SCLC-OE-exo increased the migration and tube formation ability of ECs, whereas SCLC-KD-CM and SCLC-KD-exo had inhibitory effects. Interestingly, both SCLC- and EC-derived exosomes were internalized in H446 more rapidly than in ECs. More importantly, OE-PFN2 dramatically elevated SCLC growth and vasculature formation as well as lung metastasis in tumor xenograft models. Finally, we found that PFN2 activated Smad2/3 in H446 and pERK in ECs, respectively. Taken together, our study revealed the role of PFN2 in SCLC development and metastasis, as well as tumor angiogenesis through exosomes, providing a new molecular target for SCLC treatment.

Well-timed progression of primordial folliculogenesis is essential for mammalian female fertility. Progesterone (P4) inhibits primordial follicle formation under physiological conditions; however, P4 receptor that mediates this effect and its underlying mechanisms are unclear. In this study, we used anin vitroorgan culture system to show that progesterone receptor membrane component 1 (PGRMC1) mediated P4-induced inhibition of oocyte meiotic prophase I and primordial follicle formation. We found that membrane-impermeable BSA-conjugated P4 inhibited primordial follicle formation similar to that by P4. Interestingly, PGRMC1 and its partner serpine1 mRNA-binding protein 1 were highly expressed in oocytes in perinatal ovaries. Inhibition or RNA interference of PGRMC1 abolished the suppressive effect of P4 on follicle formation. Furthermore, P4-PGRMC1 interaction blocked oocyte meiotic progression and decreased intra-oocyte cyclic AMP (cAMP) levels in perinatal ovaries. cAMP analog dibutyryl cAMP reversed P4–PGRMC1 interaction-induced inhibition of meiotic progression and follicle formation. Thus, our results indicated that PGRMC1 mediated P4-induced suppression of oocyte meiotic progression and primordial folliculogenesis by decreasing intra-oocyte cAMP levels.

Multidrug resistance (MDR) is a major obstacle to cancer chemotherapy efficacy. In the present study, 6‑O‑angeloylplenolin repressed the overexpression of ATP binding cassette subfamily B member 1 (MDR1) and increasing the intracellular concentration of anticancer drugs. A reduction in P‑glycoprotein expression (encoded by MDR1) was observed in parallel with a decline in mRNA expression in vincristine‑resistant HCT (HCT‑8/VCR) cells treated with 6‑O‑angeloylplenolin. In addition, 6‑O‑angeloylplenolin suppressed the activity of the MDR1 gene promoter. Treatment with 6‑O‑angeloylplenolin also decreased the amount of the specific protein complex that interacted with the MDR1 gene promoter in HCT‑8/VCR cells, potentially leading to the suppression of MDR1 expression. Treatment with 6‑O‑angeloylplenolin inhibited the nuclear translocation of Y‑box binding protein‑1 in HCT‑8/VCR cells treated with 6‑O‑angeloylplenolin, contributing to the negative regulation of MDR1. Finally, 6‑O‑angeloylplenolin reversed VCR resistance in an HCT/VCR xenograft model. In conclusion, 6‑O‑angeloylplenolin exhibited a MDR‑reversing effect by downregulating MDR1 expression and could represent a novel adjuvant agent for chemotherapy.

Meriones unguiculatus (Gerbillinae, Rodentia) is widely used as an animal model of human disease. Here, we provide the first report of the complete mitochondrial genome sequence of M. unguiculatus (GenBank accession Nos. KF425526 and NC_023263). The sequence contained the conserved vertebrate pattern of 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and 1 major noncoding region. We identified one extended termination-associated sequence and one conserved sequence block in the non-coding region. The putative origin of replication for the light strand (O_L) was 35 bp long. The O_L stem and adjacent sequences were highly conserved, but the loop region differed from those of other rodent species. Base composition and codon usage of the 13 protein-coding genes in M. unguiculatus were compared with those of 23 rodent species with previously sequenced mitochondrial genomes. An A+T content of 63.0% was present in M. unguiculatus; this is similar to the Murinae average (62.4 ± 0.8%) and falls between the average for Mus musculus (63.1 ± 0.1%) and Rattus sp (61.7 ± 0.4%). The AT and GC skew values of M. unguiculatus were 0.035 and -0.28, respectively, similar to those of Cricetinae species (0.057 ± 0.05 and -0.31 ± 0.05). The codon families exhibited similar abundance in all 24 species. Analysis of phylogenetic relationships with 23 other rodent species using neighbor-joining and maximum likelihood protocols and the 12 protein-coding regions on the H strand showed that M. unguiculatus should be classified as genus Meriones, sub-family Gerbillinae, family Muridae.

Understanding the genetic quality of the gerbil, Meriones meridianus, plays an important role in the study of medical biology. However, no effective system has been established for evaluating a population’s genetic diversity to date. In the present study, we established a set of reasonable evaluative systems based on microsatellite markers of the Mongolian gerbil by using the method of cross-amplification of species. Following electrophoresis analysis, short tandem repeat (STR) scanning, and sequencing, 11 microsatellite loci were identified by matching the criteria characteristics and were used to evaluate the genetic diversity of two stocks of Meriones meridianus: Meriones meridianus jei Wang, 1964 (M. m. jei) and Meriones meridianus cryptorhinus Blanford, 1875 (M. m. cryptorhinus) from Xinjiang, China. The microsatellite loci screened were highly polymorphic and were suitable for genetic quality control of Meriones meridianus. In addition, the quality of the non-bred M. m. jei and M. m. cryptorhinus strains in our study is sufficient for them to be promising stocks in the future for the farmed animal industry.