lncRNA H19 regulates epithelial–mesenchymal transition and metastasis of bladder cancer by miR-29b-3p as competing endogenous RNA

Abstract

Accumulating evidences indicate that long noncoding RNAs (lncRNAs) might play important roles in tumorigenesis and metastasis. EMT (epithelial-to-mesenchymal transition) is considered as a critical step in invasion and metastasis of various tumors including bladder cancer (BC). Recent researches have showed that lncRNA H19 is implicated in metastasis through regulating EMT and the reverse MET (mesenchymal-to-epithelial transition). However, underlying mechanisms remain largely unknown. Here, we screened lncRNA and mRNA expression profiles of BC with microarray assay. We found that H19 and DNMT3B displayed a higher co-expression in BC tissues and cells. Functionally, we demonstrated that H19 could increase proliferation, invasion and migration, regulate EMT as well as rearrange cytoskeleton of BC cells in vitro. Moreover, ectopic expression of H19 promoted tumorigenesis, angiogenesis and pulmonary metastasis in vivo, whereas knockdown of H19 has a contrary role in vivo and in vitro. Mechanistically, we proved that H19 could directly bind to miR-29b-3p (miR-29b) and derepress the expression of target DNMT3B. H19 and miR-29b-3p showed a co-localization. More importantly, up-regulating H19 antagonized miR-29b-3p-mediated proliferation, migration and EMT suppression in BC cells. Furthermore, H19 knockdown partially reversed the function of miR-29b-3p inhibitor on DNMT3B and facilitated miR-29b-3p-induced MET. Taken together, we demonstrated for the first time that H19 might function as ceRNA (competing endogenous RNA) for miR-29b-3p and relieve the suppression for DNMT3B, which led to EMT and metastasis of BC. Our findings highlight a novel mechanism of H19 in progression of BC and provide H19/miR-29b-3p/DNMT3B axis as a promising therapeutic target for BC.

Ginsenoside 20(S)-Rg3 Prevents PKM2-Targeting miR-324-5p from H19 Sponging to Antagonize the Warburg Effect in Ovarian Cancer Cells

“…The competitive binding of H19 to miR-324-5p rescued PKM2 from being H19 was overexpressed in various cancers including ovarian cancer, and capable of stimulating cancer cell cycle progression, proliferation, migration and invasion [24,25]. H19 facilitated tumor development and progression partly via sponging microRNA to recover the expression of microRNA-targeted genes [26][27][28]. Recently H19 was found to promote glucose metabolism and cell growth in malignant melanoma via competitively binding miR106a-5p to release E2F3 [29].…”

The association of polymorphisms in lncRNA-H19 with hepatocellular cancer risk and prognosis

“…The lncRNA- H19 , located on chromosome 11p15.5 [9], was reported to be one of the major genes in cancer [10]. Many studies have reported that H19 as an oncogene lncRNA in multiple cancers, such as, colorectal cancer [11], gastric cancer [12], breast cancer [13], bladder cancer [14], and so on. In addition, recent researches have proved that lncRNA- H19 plays important role in cancer initiation, progression, metastasis, and indicates poor prognosis and promotes tumor growth [11,15,16].…”

H19 contributes to poor clinical features in NSCLC patients and leads to enhanced invasion in A549 cells through regulating miRNA‑203‑mediated epithelial‑mesenchymal transition

“…Accumulative studies have revealed that lncRNA H19 mediate EMT by functioning as a sponge for the miRNAs in a variety of cancers (24–27). Recently, miR-203 was reported to play a crucial role in the EMT core network, which functions as a switch controlling epithelial cell plasticity during cancer progression (28).…”