MicroRNA‐494‐3p facilitates the progression of bladder cancer by mediating the KLF9/RGS2 axis

Abstract

Bladder cancer (BC) is a familiar malignancy with high morbidity and mortality. The effect of treatment is unsatisfactory after the metastasis and invasion of BC. Hence, more studies should be carried out to explore the metastasis of BC. RT‐qPCR or/and western blot was conducted to evaluate miR‐494‐3p, KLF9, and RGS2 expression. Cell proliferation and invasion were estimated by MTT assay and transwell assay, respectively. Cell migration was tested by wound healing assay and transwell assay. Dual‐luciferase reporter gene assay was employed to validate the interplay between miR‐494‐3p and KLF9 mRNA. The interaction between KLF9 and RGS2 promoter was verified using dual‐luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) assay. miR‐494‐3p expression was upregulated, whereas KLF9 and RGS2 were downregulated in BC cells. miR‐494‐3p inhibition was competent to limit the growth of BC cells. KLF9 knockdown abolished the miR‐494‐3p depletion‐mediated inhibitory growth of BC cells. Mechanistically, we found that KLF9 was a downstream gene of miR‐494‐3p and could bind to the promoter region of RGS2 to promote the expression of RGS2. Moreover, RGS2 knockdown abrogated the suppressive effects of miR‐494‐3p knockdown on the proliferation, migration, and invasion of BC cells. Notably, miR‐494‐3p inhibition obstructed the tumor growth in nude mice. miR‐494‐3p silencing inhibited the progression of BC by regulating the KLF9/RGS2 axis in vitro and in vivo, which laid the foundation for experiments of miR‐494‐3p in BC and provided therapeutic targets for BC.

Mechanism of KLF9 in airway inflammation in chronic obstructive pulmonary

“…However, when it comes to its interaction with miRNAs, most studies are illustrative of miRNAs‐mediated negative regulation of KLF9. A case in point is that miR‐494‐3p is the upstream gene that represses KLF9 expression in bladder cancer 39 . By contrast, our study initially identified that miR‐494‐3p was a downstream target of KLF9 and KLF9 positively regulated miR‐494‐3p.…”

“…A case in point is that miR‐494‐3p is the upstream gene that represses KLF9 expression in bladder cancer. 39 By contrast, our study initially identified that miR‐494‐3p was a downstream target of KLF9 and KLF9 positively regulated miR‐494‐3p. Interestingly, miR‐494‐3p can be activated by oxidative stress in COPD cell model and its knockdown rescues cell senescence and inflammation.…”

Transcription factor KLF9 inhibits the proliferation, invasion, and migration of pancreatic cancer cells by repressing KIAA1522

“…[31][32][33][34][35] On another note, KLF9 serves as a tumor promoter in nasopharyngeal and ovarian cancers. 36,37 Mechanistically, KLF9 is controlled by microRNAmediated negative regulation or involved in lncRNA-mediated ceRNA network to play a role in cancers, 38,39 and hypermethylation of the KLF9 promoter is instrumental in the prediction of cancer prognosis, 40 and KLF9 mediates the transcription of reactive oxygen species to regulate premalignant hyperplasia. 41 In this study, we uncovered that KLF9 was downregulated in PC cells relative to noncancerous cells and the incorporation of KLF9 in PC cells promoted the proliferation, invasion, and migration.…”

LncRNA SLC7A11-AS1 promotes the progression of hepatocellular carcinoma by mediating KLF9 ubiquitination

“…Transcription factor KLF9 has been widely explored in tumors. For instance, miRNA-494-3p decreased KLF9 expression to facilitate the progression of bladder cancer [38]; KLF9 regulated by TPTEP1/miR-548d-3p axis inhibited cell migration and invasion of gastric cancer [39]; miR-889-5p could downregulate KLF9 expression to accelerate HCC progression [40], which demonstrated that KLF9 had abnormally low expression and KLF9 overexpression generated the suppressing in uence on the progression of tumors including HCC. Here, we explored the downstream target of KLF9.…”