LncRNA CARLo-7 facilitates proliferation, migration, invasion, and EMT of bladder cancer cells by regulating Wnt/β-catenin and JAK2/STAT3 signaling pathways

Abstract

Background: Aberrant expression of long noncoding RNAs (lncRNAs) has been found to enroll in the initiation and progression of bladder cancer (BC). Earlier results show cancer-associated region long noncoding RNA-7 (CARLo-7) can be a prognostic marker for BC, but its biological function and the underlying mechanism is still to be discovered. Our study aims to explore the effects of CARLo-7 on the initiation and progression of BC and the potential mechanisms.Methods: The expression of CARLo-7 in BC tissues and cell lines was determined by quantitative real-time polymerase chain reaction (qRT-PCR). T24 and HT1197 cells were transfected with CARLo-7 expression vector or sh-CARLo-7, then cell viability assay, BrdU assay, flow cytometry, Transwell cell migration, and invasion assay, and western blot were conducted to evaluate cell proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT).Results: CARLo-7 was dramatically upregulated in BC tissues and cell lines. Silencing CARLo-7 by sh-CARLo-7 significantly suppressed proliferation and induced apoptosis of BC cells, while enforced CARLo-7 expression promoted cell proliferation. Meanwhile, silencing CARLo-7 attenuated migration, invasion, and EMT of BC cells, while CARLo-7 overexpression had the contrary effects. The β-catenin, p-JAK2 and p-STAT3 levels were decreased by CARLo-7 knockdown, while activation of Wnt/β-catenin or JAK2/ STAT3 pathways abolished the effects of CARLo-7 knockdown on cell proliferation and migration.Conclusions: Collectively, CARLo-7 plays a critical role in regulating BC development by regulating cell proliferation, migration, invasion, and EMT through Wnt/β-catenin and JAK2/STAT3 signaling. Therefore, CARLo-7 might be a promising therapeutic target for BC.

LINC01315 accelerates the growth and epithelial-mesenchymal transition of colorectal cancer cells via activating the Wnt/β-catenin signal

“…Ectopic lncRNAs expressions have been implicated in cancer metastasis through the downstream effector molecules deregulation [ 32 ]. LINC01315 elevates the expression of discs large homolog 3 (DLG3) via sponging miR-211 and then delays oral squamous cell carcinoma (OSCC) progression [ 33 ].…”

STAT3 and Its Pathways Dysregulation – Underestimated Role in Urological Tumors

“…Conversely, lncRNA CARLo-7, which was established as the only bladder cancer specific lncRNA in the CARLo cluster, is dramatically overexpressed in bladder cancer cells. Silencing of CARLo-7 repressed activation of JAK/STAT and Wnt/βcatenin pathways and therefore migration, invasiveness and EMT were diminished [98].…”

Biological functions and clinical significance of long noncoding RNAs in bladder cancer

“…LncRNAs are reported to modulate autophagy [ 74 ]. ADAMTS9-AS2 inhibits BCa progression by affecting several key autophagy and apoptotic proteins [ 75 ]. Similarly, a study by Ying et al demonstrated that insufficient expression of MEG3 could activate autophagy and promote cell proliferation [ 76 ].…”

“…LSINCT5 activates Wnt/β-catenin signaling by interacting with NCYM to promote the EMT process [ 149 ]. CARLo-7 enables the proliferation, metastasis, and EMT of BCa cells by regulating the Wnt/β-catenin and JAK2/STAT3 signaling pathways [ 75 ].…”

“…The expression of SNHG16 [ 83 ], BCAR4 [ 32 ], and SLCO4A1-AS1 [ 45 ] is related to metastasis and pathological stage. In addition, the high expression levels of LINC01296 [ 155 ], Carlo-7 [ 75 ], and ROR1-AS1 [ 54 ] are correlated with advanced tumor stage, higher tumor grade, and metastasis. In contrast, the expression of MIR143HG and MIR503HG is negatively correlated with tumor grade, advanced stage, and lymph node metastasis [ 111 , 151 ].…”