RESUMO
BACKGROUND: Melanoma is an aggressive disease that is rising in incidence. Advanced melanoma is still a life-threatening disease. CircRNAs are documented to be involved in melanoma progression. But circITCH role in melanoma remains unclear. METHODS AND RESULTS: To explore the functions of circITCH in melanoma, levels of circITCH in melanoma tissues and paracarcinoma normal tissues were detected. To study the roles of circITCH in melanoma in terms of cell proliferation and migration, in vitro and in vivo experiments were performed. Mechanism study was designed to investigate the potential regulatory effect of circITCH in melanoma. Results revealed that circITCH expression was repressed in melanoma versus adjacent normal tissues. Function study showed that circITCH suppressed melanoma cell proliferation and metastasis. The mechanism study showed that circITCH-sponged miR-660 to upregulate TFCP2 and suppress melanoma progression. CONCLUSIONS: The circITCH/miR-660/TFCP2 axis is involved in melanoma progression hence circITCH can be a diagnostic biomarker as well as a target for treating melanoma.
Assuntos
Proteínas de Ligação a DNA , Melanoma , MicroRNAs , RNA Circular , Fatores de Transcrição , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Melanoma/patologia , MicroRNAs/genética , Metástase Neoplásica , RNA Circular/genética , Proteínas Repressoras , Fatores de Transcrição/genética , Ubiquitina-Proteína LigasesRESUMO
Globally, ovarian cancer is the 2nd most frequent cause of gynecologic-associated cancer fatalities among women. It has an unfavorable prognosis. There is a need to elucidate on the mechanisms involved in ovarian cancer progression and to identify novel cancer targets. We investigated and verified AHNAK contents in ovarian cancer tissues and corresponding healthy tissues. Then, we overexpressed AHNAK in vitro and in vivo to establish the roles of AHNAK in ovarian cancer cell proliferation and metastasis. Finally, we evaluated the possible molecular mechanisms underlying. We established that AHNAK was downregulated in ovarian cancer. Elevated AHNAK contents in ovarian cancer cell lines remarkably repressed ovarian cancer cell growth, along with metastasis in vitro, as well as in vivo. Moreover, AHNAK suppressed the progress of ovarian cancer partly via dampening the Canonical Wnt cascade. Therefore, AHNAK may be a biomarker and treatment target for ovarian cancer.
Assuntos
Neoplasias Ovarianas , Feminino , Humanos , Neoplasias Ovarianas/patologia , Via de Sinalização Wnt , beta Catenina/genética , beta Catenina/metabolismo , Proliferação de Células , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Movimento Celular , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas de Neoplasias/metabolismoRESUMO
Ovarian cancer is a major gynecologic cancer and common cause of gynecologic cancer death worldwide. However, the molecular mechanisms of ovarian cancer progression are still unclear. circular RNAs (circRNAs) are recently reported to be involved in cancer progression regulation but the potential functions of circRNAs in ovarian cancer remains unknown. In this study, we explored the expression of circKIF4A in ovarian cancer tissues. Then, a series of experiments were conducted to investigate how circKIF4A functioned in ovarian cancer in vitro and in vivo. The results revealed that circKIF4A was highly expressed in ovarian cancer tissues. Knockdown of circKIF4A suppressed cell proliferation and migration in ovarian cancer. Subsequent mechanism study revealed that circKIF4A acted as a competitive endogenous RNA (ceRNA) to promoted ovarian cancer progression by sponging miR-127 and upregulated the expression of Junctional adhesion molecule 3 (JAM3). Therefore, circKIF4A could be a novel biomarker and therapeutic target for ovarian cancer.