NACC1, as a Target of MicroRNA-331-3p, Regulates Cell Proliferation in Urothelial Carcinoma Cells

Abstract

The nucleus accumbens-associated protein 1 (NACC1) is a transcription factor constitutively expressed in the urothelium, where it regulates cell growth, senescence, autophagy, and epithelial-mesenchymal transition. microRNA (miRNA) constitutes a class of small non-coding RNAs which are involved in cell proliferation, differentiation, and progression of tumors. miRNAs and their target molecules are utilized for molecular diagnosis of urothelial carcinoma. NACC1 is one of several putative target molecules of miR-331-3p, and is associated with cell proliferation in cancers such as prostate and cervical cancer. Functional experiments involving miR-331-3p and its target molecule NACC1 were conducted using the urothelial carcinoma (UC) cell lines, T24, UMUC6, and KU7. Furthermore, quantitative reverse transcription polymerase chain reaction and immunostaining were performed to evaluate the expression of NACC1 in UC derived from transurethral resection of bladder tumor (TUR-Bt) specimens. The methane thiosulfonate (MTS) assay revealed that cell proliferation was significantly reduced after transient transfection of miR-331-3p precursor and/or NACC1 siRNA in UC cells. Cell senescence via cell cycle arrest at the G1 phase was induced by NACC1 inhibition. On the other hand, suppression of NACC1 induced cell migration and invasion abilities. Immunohistochemical analysis of TUR-Bt specimens revealed that over 70% of UC cells presented strongly positive results for NACC1. In contrast, normal urothelial cells were weakly positive for NACC1. It was also found that NACC1 expression was lower in invasive UC cells than in non-invasive UC cells. Loss of NACC1 induced vessel invasion in invasive UC tissues. The present results indicate that NACC1 regulated by miR-331-3p contributes to cell proliferation, and is involved in cell migration and invasion. This suggests that NACC1 can serve as a potential target molecule for the prediction and prognosis of UC, and can contribute to effective treatment strategies.

MicroRNA‐331‐3p inhibits epithelial‐mesenchymal transition by targeting ErbB2 and VAV2 through the Rac1/PAK1/β‐catenin axis in non‐small‐cell lung cancer

“…Our previous study showed that miR‐331‐3p promotes proliferation and metastasis of hepatocellular carcinoma, and other researchers found similar effects of miR‐331‐3p in pancreatic cancer . However, other researchers discovered antitumor functions of miR‐331‐3p in urothelial cancer, gastric cancer, and cervical cancer . The functions of miR‐331‐3p in NSCLC were also ambiguous, and little was known about the targets and signaling pathways regulated by miR‐331‐3p in NSCLC.…”

miR-19a-3p Promotes Tumor-Relevant Behaviors in Bladder Urothelial Carcinoma via Targeting THBS1

“…Zhang et al [ 13 ] confirmed that the miR-30a level is decreased in BLCA, and miR-30a hinders the progression of BLCA cells. Therefore, based on the regulatory effect of miRNA on the progression of BLCA, numerous miRNAs are promising molecular therapeutic targets of BLCA, such as miR-133b [ 14 ], miR-429 [ 15 ], and miR-331-3p [ 16 ]. However, it is still unknown whether miR-19a-3p is dysregulated in BLCA and whether it has the function of regulating the progression of BLCA.…”

A New Case of de novo Variant c.892C>T (p.Arg298Trp) in NACC1: A First Case Report From China

“…As a transcriptional repressor, NAC1 regulates cell growth, senescence, epithelial–mesenchymal transition, and autophagy. NAC1 prevents cytotoxicity by stabilizing hypoxia-inducible factor-1α and regulating glucose levels, thereby playing a role in the hypoxic tumor environment ( 31 ). NAC1 forms a homodimer or heterodimers with other binding partners through the BTB/POZ domain and exerts transcriptional inhibition through the recruitment of histone deacetylase ( 32 ).…”