QKI‐6 inhibits bladder cancer malignant behaviours through down‐regulating E2F3 and NF‐κB signalling

Abstract

Quaking homolog (QKI) is a member of the RNA‐binding signal transduction and activator of proteins family. Previous studies showed that QKI possesses the tumour suppressor activity in human cancers by interacting with the 3'‐untraslated region (3'‐UTR) of various gene transcripts via the STAR domain. This study first assessed the association of QKI‐6 expression with clinicopathological and survival data from bladder cancer patients and then investigated the underlying molecular mechanisms. Bladder cancer tissues (n = 223) were subjected to immunohistochemistry, and tumour cell lines and nude mice were used for different in vitro and in vivo assays following QKI‐6 overexpression or knockdown. QKI‐6 down‐regulation was associated with advanced tumour TNM stages and poor patient overall survival. QKI‐6 overexpression inhibited bladder cancer cell growth and invasion capacity, but induced tumour cell apoptosis and cell cycle arrest. Furthermore, ectopic expression of QKI‐6 reduced tumour xenograft growth and expression of proliferation markers, Ki67 and PCNA. However, knockdown of QKI‐6 expression had opposite effects in vitro and in vivo. QKI‐6 inhibited expression of E2 transcription factor 3 (E2F3) by directly binding to the E2F3 3'‐UTR, whereas E2F3 induced QKI‐6 transcription by binding to the QKI‐6 promoter in negative feedback mechanism. QKI‐6 expression also suppressed activity and expression of nuclear factor‐κB (NF‐κB) signalling proteins in vitro, implying a novel multilevel regulatory network downstream of QKI‐6. In conclusion, QKI‐6 down‐regulation contributes to bladder cancer development and progression.

MiR-362-5p, Which Is Regulated by Long Non-Coding RNA MBNL1-AS1, Promotes the Cell Proliferation and Tumor Growth of Bladder Cancer by Targeting QKI

“…Additionally, the expression levels of QKI and macroH2A1.1 were decreased in bladder cancer tissues (Sporn et al, 2009;Novikov et al, 2011). It also reported that QKI-6 inhibits bladder cancer cell proliferation through downregulating E2F3 and NF-kB pathway (Shi et al, 2019). Yang et al stated that QKI negatively regulates the expression levels of Cyclin D and c-Fos and positively regulates p27 expression to block the cell cycle progress.…”

<p>Circular RNA CircPRMT5 Accelerates Proliferation and Invasion of Papillary Thyroid Cancer Through Regulation of miR-30c/E2F3 Axis</p>

“…25 E2F3 collaborates with NF-κB pathway to aggravate bladder cancer. 26 Additionally, E2F3 also promotes ovarian cancer growth and chemo-sensitivity. 27 Nevertheless, E2F3 function in PTC is not clear.…”

CAFs‐derived MFAP5 promotes bladder cancer malignant behavior through NOTCH2/HEY1 signaling

“…Generally, solid tumors develop due to cooperation between alterations of multiple oncogenic drivers and not a single driver 43 . Our previous study demonstrated that QKI is a tumor suppressor in bladder cancer 22 . QKI posttranscriptionally regulates target mRNA expressions as an RNA‐binding protein 44 .…”

“…Solid tumors are largely caused by collaboration between alterations of multiple oncogenic drivers 43 . Our previous study showed that QKI inhibits the progression of bladder cancer 22 . Results from immunofluorescence staining showed that downregulation of QKI, together with upregulation of MFAP5, is associated with advanced bladder cancer and poor prognosis.…”

“…Previous studies demonstrated that MFAP5 can promote the proliferation and metastasis of malignant tumors, including breast cancer, oral tongue squamous cell carcinoma, and ovarian cancer, through multiple signaling pathways 7,16,20,21 Quaking homolog (QKI) is a member of the RNA‐binding signal transduction and activator of proteins family. Our previous study demonstrated a suppressive role for QKI in bladder cancer 22 and renal cell carcinoma 23 . As an RNA‐binding protein, QKI posttranscriptionally regulates the target mRNA expression 24,25 …”