RESUMEN
Objectives: Cigarette smoking is involved in the pathogenesis of head and neck squamous cell carcinoma (HNSCC). However, the underlying molecular mechanisms of cigarette smoking-induced HNSCC carcinogenesis are unclear and may involve cancer stem-like cell generation. We examined the effects of cigarette smoke condensate (CSC) on the formation of cancer stem-like cells, which are rich in octamer-binding transcription factor (OCT)-4, inhibitor of differentiation 1 (ID1), nuclear factor (NF)-κB, and B lymphoma Mo-MLV insertion region 1 homolog (BMI-1). Materials and Methods: We used in vitro, in vivo, and archival human HNSCC tissue analysis to evaluate the effects of CSC on cancer stem-like cell formation. Results: We found that CSC regulated OCT-4 expression, which subsequently regulated ID1 and NF-κB, at the promoter, mRNA, and protein levels in vitro. Furthermore, OCT-4 knockdown with siRNA reduced ID1 expression. ID1 and NF-κB synergistically increased the expression of BMI-1 and stimulated keratinocyte sphere generation. In vivo, ID1 and NF-κB acted together to generate malignant xenograft tumors, which were aggressive locally and systemically metastatic. Clinical data confirmed that ID1- and NF-κB-positive patients had poor clinical outcomes and 5-year disease-free survival. Conclusion: Our data suggest that smoking cigarettes promoted cancer stem-like cell generation in the head and neck area via the OCT-4/ID1/NF-κB/BMI-1 signaling pathway.
RESUMEN
The taxonomic status of some genera within the Phasianidae remains controversial. To demonstrate the phylogenetic relationships of four endemic genera (Tetraophasis, Ithaginis, Crossoptilon and Chrysolophus) and other 11 genera of Phasianidae in China, a total of 1070 nucleotides of mitochondrial DNA (mtDNA) control-region genes were sequenced. There are 376 variable sites including 345 parsimony sites. The genetic distance ranged from 0.067 (Chrysolophus and Phasianus) to 0.181 (Perdix and Bambusicola) among the 15 genera. Maximum likelihood method was used to construct a phylogenetic tree, which grouped all the genera into two deeply divergent clades. Perdix was shown to be a non-partridge genus. Alternatively, it appears ancestral to either partridges or pheasants. The sibling taxa of the four endemic genera were Lophophorus, Tragopan, Lophura and Phasianus, respectively. Calibrated rates of molecular evolution suggested that the divergence time between the four genera and related taxa was 4.00-5.00 million years ago, corresponding to the Pliocene. Considering their molecular phylogenetics, fossil and geographical distribution patterns, the four endemic genera might have originated in the southwestern mountains in China.