AB122. The structure and function of NKAIN2—a candidate tumor suppressor

Abstract

Objective: To evaluate the clinical efficacy of bladder hydrodistention and intravesical sodium hyaluronate in the treatment of interstitial cystitis (IC). Methods: Twenty-one patients with IC received intravesical sodium hyaluronate therapy under nerve block or intravenous anesthesia. Bladders were perfused with 100 cmH 2 O perfusion pressure and expanded for 10 min and were later injected with 40 mg/50 mL sodium hyaluronate through the catheter. After 1 h, the perfusion fluid was released. Perfusion was applied once per week, 4 to 6 times as a course of treatment. Results: Under anesthesia, the average bladder capacity was 191.62±88.67 mL, and after bladder expansion, the bladder capacity reached 425.33±79.83 mL (P=0.000). There were two suspected bladder ruptures after bladder expansion at 6.5 and 7.2 min. After 10 min of bladder expansion, there were 19 cases of significantly gross hematuria. After treatment, the catheters of 17 patients were removed at 24 h; for the two cases of hematuria, catheters were removed at 72 h and for the two cases of suspected bladder rupture, catheters were removed after 4 days. After catheter removal, the pain threshold significantly decreased, and the maximum urinary output increased slightly. Compared with values before treatment, the day before the second injection of sodium hyaluronate, the frequency of urination decreased significantly (32.8 vs. 18.5 times/24 h), the maximum urinary output increased significantly (86.7 vs. 151.9 mL), the pain decreased significantly (8.7 vs. 3.0), and the O'Leary-Sant IC score and quality of life score were significantly decreased (30.0 vs. 17.0 and 5.9 vs. 2.4, respectively) (P=0.000). Conclusions: Bladder hydrodistention under anesthesia for patients with severe intractable IC produces immediate effectiveness; sodium hyaluronic infusion can alleviate frequent urination and pain, and the efficacy was positively correlated with the duration of treatment. Objective: The deletion of chromosomal region 6q was commonly found in several types of human cancers, although the tumour suppressor genes (TSGs) located within this genomic region are not well established. Our recent work detected recurrent chromosomal truncation at the Na+/K+ transporting ATPase interacting 2 (NKAIN2) gene, which was also found to be truncated in leukemia and lymphoma, suggesting that NKAIN2 is potentially one of the TSGs located in the 6q commonly deleted region in human cancers. Further genetic and cellular functional are required to confirm its tumour suppressor role. Methods: We review the basic structure and biological function of NKAIN2 by published articles to find out existing evidence to support its role in tumorigenesis, emphasizing its role in prostate cancer. Results: NKAIN2 gene consists of eight coding exons that span approximately 1 Mb of genomic DNA on chromosome 6q and there are four main splice variants. The function ofPrinted Abstracts

EWSR1/FUS-NFATc2 rearranged round cell sarcoma: clinicopathological series of 4 cases and literature review

“…We speculate that this is likely active but of unclear clinical significance, as ACTN2 has a strong N-terminal homodimerization domain, the prerequisite for ALK activation by fusion (34), and additionally ALK has been reported to be expressed in a high percentage of Ewing Sarcomas (35). Regarding the candidate FOXO1-NKAIN2 fusion, NKAIN2 is a poorly characterized candidate tumor suppressor gene; fusions and translocations that have been previously reported for this protein are typically either inactivating or out-of-frame (36). FOXO1 fusions to PAX3 or PAX7 include the FOXO1 C-terminal transcriptional activation domain (TAD), aberrantly activating PAX3/7 targets (37).…”

The Fas Signaling Pathway Is a Common Genetic Risk Factor for Severe Cutaneous Drug Adverse Reactions Across Diverse Drugs

“…A previous report showed that a chromosomal translocation involving this gene was a cause of lymphoma. 19 Angiopoietin 2 encoded by ANGPT2 is an antagonist of angiopoietin 1 and thus disrupts its vascular remodeling ability which may induce endothelial cell apoptosis. 20 However, so far, there has been no report to show the association between SCAR or drug adverse reaction and NKAIN2 or ANGPT2 .…”

Downregulation of microRNA-181d had suppressive effect on pancreatic cancer development through inverse regulation of KNAIN2

“…18,19 Therefore, it is very likely that the role of miR-181d, whether as oncogene or tumor suppressor, may be well determined by inverse regulation on its downstream target genes in different cancers. As for gene of NKAIN2, though it was implicated in previous studies that it might act as tumor suppressor, 15,16 or oncogene in human cancer, 17 our study is the first one to reveal its predominant tumor-suppressive role, as well as its close correlation with miR-181d regulation in pancreatic cancer.…”

“…15 In various human cancers, NKAIN2 gene is found to be recurrently truncated, possibly located in the 6q commonly deleted region. 15 It was suggested that NKAIN2 might act as a tumor suppressor in human cancer as it induces chromosome loss, mutation, and promoter methylation. 15,16 Interestingly, in another human cancer, NKAIN2 was found to be highly expressed in cancer cells of neuroblastoma and subsequently downregulated in retinoic acid differentiation, thus suggesting an oncogenic role in neuroblastoma.…”

“…15 It was suggested that NKAIN2 might act as a tumor suppressor in human cancer as it induces chromosome loss, mutation, and promoter methylation. 15,16 Interestingly, in another human cancer, NKAIN2 was found to be highly expressed in cancer cells of neuroblastoma and subsequently downregulated in retinoic acid differentiation, thus suggesting an oncogenic role in neuroblastoma. 17 Nevertheless, the role of NKAIN2 in human pancreatic cancer, whether to be tumor suppressor or oncogene, was never elucidated.…”