Research Paper Volume 12, Issue 24 pp 25845—25864

The long noncoding RNA LINC01140/miR-140-5p/FGF9 axis modulates bladder cancer cell aggressiveness and macrophage M2 polarization

Shuiqing Wu1, , Ran Xu1, , Xuan Zhu1, , Haiqing He1, , Jinhua Zhang1, , Qi Zeng1, , Yinhuai Wang1, , Xiaokun Zhao1, ,

  • 1 Department of Urology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, People’s Republic of China

Received: February 24, 2020       Accepted: September 9, 2020       Published: November 21, 2020
How to Cite

Copyright: © 2020 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


MIBC (muscle invasive bladder cancer) only accounts for only a minority of bladder cancers, however, the disease-specific and overall survival rates of patients with MIBC are low. Macrophage M2 polarization has been reported to be associated with poorer prognosis in bladder cancer. Through cancer bioinformatics and experimental analyses, FGF9 was found to be upregulated in MIBC tissues. FGF9 knockdown in T24 cells strongly suppressed the viability, migratory capacity, and invasive capacity of cells; culture with medium from FGF9 knockdown T24 cells (si-FGF9-CM) significantly inhibited macrophage M2 polarization, while promoting M1 polarization. The long noncoding RNA (lncRNA) LINC01140 was positively correlated with FGF9 and was significantly upregulated in MIBC tissues. LINC01140 knockdown inhibited the viability, migratory capacity and invasive capacity of T24 cells; culture in si-LINC01140-CM also inhibited macrophage M2 polarization, while promoting M1 polarization. LINC01140 targeted miR-140-5p, while miR-140-5p targeted FGF9 to form a lncRNA-miRNA-mRNA axis. The effects of miR-140-5p inhibition on bladder cancer aggressiveness and macrophage M2 polarization were opposite to those of LINC01140 or FGF9 knockdown; additionally, miR-140-5p inhibition partially reversed the effects of LINC01140 knockdown on FGF9 protein levels, bladder cancer phenotype, and macrophage M2 polarization. In conclusion, LINC01140, miR-140-5p, and FGF9 form a lncRNA-miRNA-mRNA axis that modulates the bladder cancer phenotype, affects macrophage M2 polarization through the tumor microenvironment, and in turn affects bladder cancer cell aggressiveness.


MIBC: muscle invasive bladder cancer; NMIBC: non-muscle invasive bladder cancer; LncRNA: Long non-coding RNA; TME: tumor microenvironment.