kiss1-protein--human and Peritoneal-Neoplasms

Peritoneal metastasis is a critical feature and clinical challenge in epithelial ovarian cancer (EOC). We previously identified a novel long noncoding RNA (lncRNA, TC0101441) in epithelial ovarian cancer (EOC) using microarrays. However, the impact of TC0101441 on EOC metastasis and prognosis remains unclear. TC0101441 expression in EOC tissues and its correlation with clinicopathological factors and prognosis were examined. A series of in vitro and in vivo assays were performed to elucidate the roles and mechanism of TC0101441 in EOC metastasis. We found that TC0101441 levels were elevated in EOC tissues compared with those in normal controls and significantly correlated with an advanced clinical stage and lymph node metastasis. TC0101441 was determined to be an independent prognostic predictor of overall survival (OS) and disease-free survival (DFS). Furthermore, loss-of-function assays showed that TC0101441 promoted the invasive and metastatic capacities of EOC cells both in vitro and in vivo. Mechanistically, the prometastatic effects of TC0101441 were linked to the induction of epithelial-mesenchymal transition (EMT). Importantly, KiSS1 was identified as a downstream target gene of TC0101441 and was downregulated by TC0101441 in EOC cells. After TC0101441 was silenced, the corresponding phenotypes of EOC cell invasion and EMT were reversed by the overexpression of KiSS1. Taken together, our data suggest that TC0101441 functions as a potential promigratory/invasive oncogene by promoting EMT and metastasis in EOC through downregulation of KiSS1, which may represent a novel prognostic marker and therapeutic target in EOC.

Topics: Animals; Apoptosis; Biomarkers, Tumor; Carcinoma, Ovarian Epithelial; Cell Movement; Cell Proliferation; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Neoplastic; Humans; Kisspeptins; Lymphatic Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Ovarian Neoplasms; Peritoneal Neoplasms; Prognosis; RNA, Long Noncoding; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Cancer research is currently focused on blocking the metastatic process at its early steps. Some particularly attractive targets are metastasis suppressor genes, which control cancer cell dissemination. The aim of this study was to clarify the relationship between the expression of KiSS1, a metastasis suppressor gene, and disease progression in colorectal cancer patients. One-hundred and seventy-five patients who underwent surgery for colorectal cancer were enrolled in this study. We analyzed KiSS1 mRNA expression by real-time reverse transcription PCR in colorectal cancer tissue and paired adjacent normal mucosa. KiSS1 protein expression in early- and advanced-stage colorectal cancer samples was determined by immunohistochemical analysis. Decreased KiSS1 expression was significantly associated with lymph node metastasis and was an independent prognostic factor. Logistic regression analysis revealed that decreased KiSS1 expression was an independent risk factor for lymph node metastasis. Immunohistochemical analysis indicated that KiSS1 was highly expressed in the cell cytoplasm of early-stage colorectal cancer cells. The loss of KiSS1 appears to correlate with the progression of lymph node metastasis. An assessment of KiSS1 expression may assist in the accurate colorectal cancer diagnosis and may contribute to predict clinical outcomes.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Child; Colorectal Neoplasms; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Kisspeptins; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Peritoneal Neoplasms; Prognosis; Prospective Studies; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Survival Rate; Young Adult