Long Noncoding RNA <i>HAND2-AS1</i> Suppresses Cell Proliferation, Migration, and Invasion of Bladder Cancer via <i>miR-17-5p</i> / <i>KLF9</i> Axis

Abstract

Bladder cancer (BC) is the most common type of malignant tumor in the genitourinary system. Through the microarray analysis of clinical samples, long noncoding RNA <i>HAND2-AS1</i> expression was found to be downregulated in BC tissues. However, the function of <i>HAND2-AS1</i> on BC and underlying mechanism are unclear. In this study, the correlations of <i>HAND2-AS1</i> with clinicopathological parameters in BC patients were determined. The gain- and loss-of-function experiments were conducted to examine the role of <i>HAND2-AS1</i> in malignant behaviors of BC cells <i>in vitro</i> and <i>in vivo</i>. Then, we paid attention to <i>miR-17-5p</i>/<i>KLF9</i> axis to illustrate the molecular mechanism. Results showed that <i>HAND2-AS1</i> was downregulated in BC tissues, and its overexpression significantly inhibited cell proliferation, migration, and invasion <i>in vitro</i>, as well as tumor growth <i>in vivo</i>. Knockdown of <i>HAND2-AS1</i> caused an opposite effect on BC cell malignancies. Furthermore, <i>miR-17-5p</i> was shown to be a direct target of <i>HAND2-AS1</i>, and it reversed the inhibitory effect of <i>HAND2-AS1</i> on BC malignancies. Also, as a downstream factor of <i>miR-17-5p</i>, <i>KLF9</i> silencing was demonstrated to mediate the role of <i>miR-17-5p</i> inhibitor in BC cell proliferation and invasion. Thus, it suggests that <i>HAND2-AS1</i> acts as a suppressor in BC development through <i>miR-17-5p</i>/<i>KLF9</i> axis.