Abstract. The target protein for Xklp2 (TPX2), a microtubuleassociated protein, can be used to evaluate more precisely the proliferative behavior of tumor cells. The abnormal expression of TPX2 in various types of malignant tumors has been reported, but less is known for cervical cancer. We studied the relationship between TPX2 expression and the biological behavior of cervical cancer. Immunohistochemistry and RT-PCR were used to detect the expression of TPX2 in cervical cancer tissues. The inhibitory effect of TPX2-siRNA on the growth of HeLa human cervical carcinoma cells was studied in vitro. TPX2 expression was found to be significantly higher in cervical carcinoma compared to normal cervical tissues and CIN. The expression of TPX2 in cervical cancer was correlated with histological grading, FIGO staging and lymph node metastasis. TPX2 RNAi in HeLa cervical cancer cells caused S-phase cell cycle arrest, induced apoptosis and inhibited cell proliferation and invasion. In conclusion, TPX2 shows potential to be used as a new marker for cervical cancer diagnosis and therapy.

The single nucleotide polymorphism (SNP) rs6983267 and cancer-associated region long non-coding RNA (CARLo-5) are associated with various human cancers. This study aimed to investigate the expression of CARLo-5 in endometrial carcinoma (EC) and its relationship with clinicopathological features and patient survival. The association of the rs6983267 SNP with EC risk and its involvement in the regulation of CARLo-5 expression in EC were investigated. The rs6983267 SNP was genotyped by polymerase chain reaction (PCR) and ligase detection reaction in 543 EC patients and 584 controls. The expression of CARLo-5 in 108 EC tissues and 66 normal endometrial tissues (NETs) was determined using quantitative real-time PCR. The genotype and allele distributions of the rs6983267 SNP differed significantly between patients and controls. There was a significant correlation between the rs6983267 genotypes and lymph node metastasis of EC patients (P = 0.026). CARLo-5 expression was significantly higher in EC tissues than in NETs (P < 0.001) and significantly associated with FIGO stage (P = 0.029) and lymph node metastasis (P = 0.030). Patients with high CARLo-5 expression had significantly shorter overall survival than those with low CARLo-5 expression (P = 0.003). The rs6983267 genotype was significantly correlated with CARLo-5 expression (P < 0.05). In conclusion, CARLo-5 was identified as a pro-oncogenic lncRNA that may play an important role in EC progression and represent a prognostic marker for EC. The expression of CARLo-5 was significantly correlated with the rs6983267 genotype associated with increased susceptibility to EC. Environ. Mol. Mutagen. 57:508-515, 2016. © 2016 Wiley Periodicals, Inc.

Ovarian cancer is one of the most common gyneacologic malignancies, with high morbidity and high mortality. Hsa-miR-122-5p (miR-122) has been reported with tumor-suppressing roles in various cancers. In this study, miR-122 was overexpressed in ovarian cancer cells, and phenotypic experiments demonstrated that miR-122 inhibited migration and invasion in SKOV3 and OVCAR3 cells. MiR-122 also suppressed epithelial mesenchymal transition (EMT), evidenced by expression changes of E-cadherin, vimentin, matrix metalloproteinase (MMP)2, and MMP14. Prolyl-4-hydroxylase subunit alpha-1 (P4HA1) was identified as a target of miR-122, and downregulated by miR-122. MiR-122-induced the elevation of migration, invasion, and EMT were recovered by P4HA1. Additionally, miR-122 restrained the tumor metastasis of SKOV3 cells in peritoneal cavity of nude mice. In summary, we demonstrated that miR-122 inhibited migration, invasion, EMT, and metastasis in peritoneal cavity of ovarian cancer cells by targeting P4HA1 for the first time, which shed lights on the discovery of miR-122 and P4HA1 as possible potential diagnostic markers and therapeutic targets for ovarian cancer.

Cisplatin is a first-line chemotherapy drug against ovarian cancer. However, its strong toxic side effects and the development of cisplatin resistance in human cancer cells seriously influence the effects of chemotherapy and quality of life in patients. Noscapine (Nos), a non-toxic benzylisoquinoline alkaloid extracted from opium, has been recently reported to have anti-cancer activity, but the mechanism of that effect has not been clearly established. In the present study, we investigated cytotoxicity of Nos in combination with cisplatin (DDP) in drug-resistant human ovarian cancer cell line SKOV3/DDP in vitro and in vivo null mice xenograft model. Cell proliferation was measured by MTT assay, flow cytometry was used to analyze cell cycle and apoptosis, protein expression of several apoptotic factors was investigated by flow cytometry and immunohistochemical method, and their mRNA expression levels were determined by real-time PCR. In vitro experiments showed that Nos significantly inhibited proliferation of SKOV3/DDP cells. DDP/Nos-combined treatment notably enhanced DDP-induced inhibition of cell proliferation and increased the pro-apoptotic effect of DDP in SKOV3/DDP cells. DDP/Nos administration increased the proportion of G2/M cells, reduced both protein and mRNA expression of anti-apoptotic factors XIAP, surviving and NF-kB, and augmented protein and mRNA levels of pro-apoptotic caspase-3. In vivo experiments revealed that Nos/DDP treatment increased the apoptotic rate of xenograft tumors in null mice. Tumor volume decreased from 1.733 ± 0.155 g in mice treated with DDP alone to 1.191 ± 0.106 g in animals treated with Nos/DDP. These observations suggest that Nos increases the anti-cancer activity of DDP against the drug-resistant ovarian cancer cell line SKOV3/DDP by modulating the cell cycle and activating apoptotic pathways. The study provides a new chemotherapy strategy for the treatment of DDP-resistant human ovarian cancer.

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