Implication of human nonmetastatic clone 23 Type 1 and its downstream gene lipocalin 2 in metastasis and patient's survival of cancer of uterine cervix

Abstract

Human nonmetastatic clone 23 Type 1 (nm23-H1) is demonstrated to have diverse roles in metastasis and survival for many cancers, which are probably caused via different impacts on its downstream genes. Our preliminary study using cDNA genechip found that lipocalin 2 seems to be a significant downstream gene of nm23-H1 in SiHa cancer cells of uterine cervix. Therefore, we investigated the expression and correlation of nm23-H1 and lipocalin 2 in cancer metastasis and their implication in recurrence and survival of cervical cancer patients. In our study, we knocked down SiHa cancer cells by short hairpin RNA for nm23-H to detect its impact on the promoter activity and gene expression of lipocalin 2. In addition to nm23-H1 knockdown, lipocalin 2 gene was overexpressed to detect their implication in metastatic phenotypes. We further used immunohistochemical methods for 100 cancer tissue cores of cervical tissue microarrays to correlate the expression of nm23-H1 and lipocalin 2 with recurrence and survival of cancer patients. Our findings showed that nm23-H1 knockdown SiHa cancer cells increased lipocalin 2 promoter activity and gene expression, then decreased cells migration and invasion. They displayed cobblestone-like appearance and decreased interior fibers. Cervical cancer patients with positive nm23-H1 and negative lipocalin 2 expression had the worst recurrence probability and overall survival. In conclusion, when nm23-H1 gene is knocked down in SiHa cervical cancer cells, cells migration and invasion decrease through elevated expression of lipocalin 2. Cervical cancer patients with positive nm23-H1 and negative lipocalin 2 should be followed and treated intensely.

Overexpression of lipocalin 2 in human cervical cancer enhances tumor invasion

“…LCN2 has also been demonstrated to inhibit invasion and angiogenesis in pancreatic cancer [ 33 ]. In a study by Wang and colleagues [ 34 ], knockdown of nm23-H1 in SiHa uterine cervical cancer cells was shown to increase LCN2 promoter activity and gene expression, thereby decreasing cell migration and invasion. These authors' investigation of the correlation between LCN2 and nm23-H1 expression in cancer metastasis suggested that the LCN2 gene is an important downstream target of nm23-H1 in SiHa cancer cells.…”

The Expression of Ribonucleotide Reductase M2 in the Carcinogenesis of Uterine Cervix and Its Relationship with Clinicopathological Characteristics and Prognosis of Cancer Patients

“…Tissue microarray sections (MaxArray with 96 tissue cores in each tissue microarray, Zymed Laboratories Inc.) were incubated with anti-RRM2 antibodies (ab57653, Abcam Inc. MA, USA). A semi-quantitative H score of RRM2 immunoreactivity was determined by multiplying the proportional score of stained cells by their immunoreactivity intensity [14], [15]. The primary clinical endpoint was to correlate the expression of RRM2 with the survival of patients with cervical cancer.…”

NGAL protects in nasopharyngeal carcinoma by inducing apoptosis and blocking epithelial‑mesenchymal transition

“…The effect of NGAL in carcinogenesis is dependent on cancer type. Upregulation of NGAL increases cell infiltration in breast, bladder, stomach, gynecological, thyroid, lung, esophageal, colon and chronic myeloid leukemia; but in pancreatic and oral cancer, it reduces cell infiltration (18,19). In addition, upregulation of NGAL can increase the proliferation of cervical cancer and lung cancer cells (20,21).…”