Characterization of a novel MICB variant in an individual from the Chinese Uyghur population, MICB*005:09, by cloning and sequencing.

A new allelic variant in MICB*005 lineage, MICB*005:09, has been identified in a male Uyghur individual recruited from Xinjiang Uyghur Autonomous Region, China by PCR-sequence-based typing (Sanger sequencing) and confirmed by cloning and sequencing. Aligned with MICB*005:03, this new allelic variant shows a synonymous T substitution at nucleotide position 8 in exon 2, corresponding to codon 3 (CAC→CAT) of the mature MICB mRNA transcript.

Receptor for activated C kinase 1 promotes cervical cancer lymph node metastasis via the glycolysis­dependent AKT/mTOR signaling.

Cervical cancer (CC), an aggressive form of squamous cell carcinoma, is characterized by early­stage lymph node metastasis and an extremely poor prognosis. The authors have previously demonstrated that patients with CC have aberrant glycolysis. The upregulation of receptor for activated C kinase 1 (RACK1) is associated with CC lymph node metastasis (LNM). However, its role in mediating aerobic glycolysis in CC LNM remains unclear. In the present study, 1H nuclear magnetic resonance analysis revealed a significant association between RACK1 expression and the glycolysis/gluconeogenesis pathway. Additionally, RACK1 knockdown inhibited aerobic glycolysis and lymphangiogenesis in vitro and suppressed CC LNM in vivo. Furthermore, protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling was identified as a critical RACK1­regulated pathway that increased lymphangiogenesis in CC. Co­immunoprecipitation, immunofluorescence and western blot analysis revealed that RACK1 activated AKT/mTOR signaling by interacting with insulin­like growth factor 1 receptor (IGF1R). POU class 2 homeobox 2 (POU2F2) bound to the RACK1 promoter and regulated its transcription, thereby functionally contributing to glycolysis and lymphangiogenesis in CC. Of note, the administration of 2­deoxy­D­glucose, which attenuates glycolysis, inhibited RACK1­induced lymphangiogenesis in CC. The correlations between RACK1, IGF1R, POU2F2 and hexokinase 2 were further confirmed in CC tissues. Thus, RACK1 plays a crucial role in CC tumor LNM by regulating glycolysis via IGF1R/AKT/mTOR signaling. Thus, the targeting of the POU2F2/RACK1/IGF1R/AKT/mTOR signaling pathway may provide a novel treatment strategy for CC.

A novel MICB allele, MICB*004:02, identifified in a western china Uyghur individual.

The novel MICB*004:02 allele differs from the closest allele MICB*004:01by a synonymous mutation in exon 2.

Effect of the SIRT3-AMPK/PPAR pathway on invasion and migration of cervical cancer cells.

SIRT3 is a mitochondrial deacetylation protein that can promote the invasion and migration of cancer cells. We explored the effects of SIRT3 regulation of the AMPK/PPAR signaling pathway on triglycerides and the invasion and metastasis of cervical cancer cells. Immunohistochemical methods were used to detect SIRT3. The expression of AMPK and PPAR proteins in different cervical lesions was analyzed in combination with clinicopathological parameters. qRT-PCR and western blotting were used to determine the expression levels of SIRT3 in the C33a and SiHa cervical cancer cell lines. To observe the effects of altering SIRT3 levels by lentivirus transfection and the consequent changes in AMPK and PPAR protein expression, oil red O staining was used to determine intracellular triglycerides, and scratch assays and Transwell chamber experiments were performed to evaluate cervical cancer cell migration and invasion. Our data indicate that SIRT3, AMPK, and PPAR protein expression levels show an increasing trend with cervical lesion severity and are related to the degree of lymph node metastasis and differentiation; moreover, increased expression of SIRT3 can promote the expression of AMPK and PPAR proteins, is beneficial to the formation of intracellular neutral fat, and enhances the ability of cells to metastasize and invade. Our results suggest that SIRT3 activates AMPK/PPAR signaling pathways involved in cancer lipid metabolism and promotes metastasis and cell invasion.

Identification of a novel allele, MICA*088N, in a Chinese Kazakh individual.

The novel MICA*088N allele has a single nucleotide mismatch in exon 4 compared to MICA*027.

Role of CXCR7 and effects on CXCL12 in SiHa cells and upregulation in cervical squamous cell carcinomas in Uighur women.

CXCR7 is involved in tumor development and metastasis in multiple malignancies. However, the function and molecular mechanisms of action of CXCR7 in human cervical cancer are still unclear. In the present study a loss of-function approach was used to observe the effects of recombinant CXCR7 specific small interfering RNA pBSilence1.1 plasmids on biological behavior including proliferative activity and invasive potential, as indicated by MTT assays with the cervical cancer SiHa cell line in vitro. Reverse transcription polymerase chain reaction and Western blotting revealed that CXCR7 was downregulated in transfected compared with control cells, associated with inhibited cell growth, invasiveness and migration. The expression of CXCR7 and CXCL12 was also determined immunohistochemically in 152 paraffin-embedded, cervical squamous cell carcinoma (CSCC) and cervical intraepithelial neoplasia (CIN), or normal cervical epithelial to assess clinico-pathological pattern and CXCR7 status with respect to cell differentiation and lymph node metastasis in Uighur patients with CSCC. CXCR7 and CXCL12 expression was higher in cervical cancer than CIN and normal cervical mucosa, especially in those with higher stage and lymph node metastasis. CXCL12 appeared to be positively regulated by CXCR7 at the post-transcriptional level in CSCC. We propose that aberrant expression of CXCR7 plays a role in carcinogenesis, differentiation and metastasis of CSCC, implying its use as a potential target for clinical biomarkers in differentiation and lymph node metastasis.