miR-221-induced PUMA silencing mediates immune evasion of bladder cancer cells

Abstract

Immune evasion of cancer cells is mainly due to the impaired transduction of apoptotic signals from immune cells to cancer cells, as well as inhibition of subsequent apoptosis signal cascades within the cancer cells. Over the past few decades, the research has focused more on the impaired transduction of the apoptotic signal from immune cells to cancer cells, rather than inhibition of the intracellular signaling pathways. In this study, miR‑221 inhibitor was transfected into bladder cancer cell lines 5637, J82 and T24 to repress the expression of miR‑221. As a result, the repression of miR‑221 on p53 upregulated modulator of apoptosis (PUMA) was abolished, resulting in increased expression of the pro-apoptotic Bax and reduced expression of the anti-apoptotic Bcl-2, which promotes apoptosis of bladder cancer cells. The expression of MMP-2, MMP-9 and VEGF-C were reduced, resulting in reduced invasiveness and infiltration capability of bladder cancer cells, thereby inhibiting the immune evasion of bladder cancer cells.

miR‐221/222 cluster expression improves clinical stratification of non‐muscle invasive bladder cancer (TaT1) patients' risk for short‐term relapse and progression

“…The miR‐221/222 cluster has been documented to promote cell proliferation and to attenuate apoptosis in epithelial cancers by targeting p27 Kip1 ( CDKN1B ), p57 Kip2 ( CDKN1C ), PUMA ( BBC3 ), BIM and BMF , as well as to facilitate cells' migration and invasiveness through the downregulation of PTEN , TIMP2 and TIMP3 inhibitors of matrix metalloproteinases, and also by triggering EMT‐like changes . Similarly in bladder tumors, miR‐221/222 cluster has been documented to suppress PTEN , PPP2R2A and PUMA expression, promoting cancer cell proliferation and survival through PI3K/Akt/mTOR pathway activation, attenuating cisplating‐induced cell death and inhibiting apoptosis . Moreover, the inhibition of miR‐221 expression in bladder cancer cells resulted to reduced expression of MMP‐2 , MMP‐9 , VEGF and mesenchymal markers (vimentin, fibronectin and N‐cadherin), suppressing cells infiltration capacity .…”

“…32 Similarly in bladder tumors, miR-221/222 cluster has been documented to suppress PTEN, PPP2R2A and PUMA expression, promoting cancer cell proliferation and survival through PI3K/Akt/mTOR pathway activation, attenuating cisplating-induced cell death and inhibiting apoptosis. [46][47][48] Moreover, the inhibition of miR-221 expression in bladder cancer cells resulted to reduced expression of MMP-2, MMP-9, VEGF and mesenchymal markers (vimentin, fibronectin and N-cadherin), suppressing cells infiltration capacity. 48,49 Finally, similar unfavorable clinical value for patients' survival outcome has been highlighted also in breast, 50 hepatocellular, 51 prostate, 52 pancreatic 53 and glioma 54 cancers.…”

LncRNAs act as prognostic and diagnostic biomarkers in renal cell carcinoma: a systematic review and meta-analysis

“…Surgery is the gold standard for localized RCC; however, this strategy provides limited benefits for patients with locally advanced or metastatic RCC; Metastatic RCC is also resistant to chemotherapy and radiotherapy; as such, new therapeutic targets should be developed. In RCC research, several genetic biomarkers, including mRNAs, such as HIF1α [4], Von Hippel-Lindau gene(VHL) [4], NOTCH1 [5], S100A6 [6], and E2F1 [7], and microRNAs (miRs), such as miR-21 [8], miR-221 [9] and miR-30a [10], have been used. Long non-coding RNAs (lncRNAs) have also been extensively investigated because of their clinical usefulness and biological properties in diagnosis, prognosis, and treatment.…”

MicroRNA-3713 regulates bladder cell invasion via MMP9

“…However, the regulation of MMP9 by miRNAs in TCC has only been shown indirectly through other miRNA-targeting proteins, e.g. p53 by miR-22136, and c-met by miR-409-3p37. We actually screened all miRNAs that target MMP9 using bioinformatics analyses, and got 26 hits altogether.…”