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. Nucleus accumbens-associated protein 1 (NACC1), one of several transcription factors, is constitutively expressed in the urothelium, wherein it regulates cell growth, senescence, autophagy, epithelial-mesenchymal transition. We previously reported that NACC1 is the target molecule of miR-331-3p and is associated with cell proliferation in prostate and cervical cancer.
Functional experiments involving miR-331-3p and its target molecule, NACC1, was analyzed using urothelial carcinoma (UC) cell lines, T24, UMUC6, and KU7. Quantitative reverse transcription polymerase chain reaction, and immunostaining were performed to evaluate the expression of miR-331-3p and NACC1 in UC derived from transurethral resection of bladder tumor (TUB-Bt) specimens.
The 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. Immunohistochemistry with TUR-Bt specimens revealed that greater than 90% of both UC and normal urothelial cells were positive for NACC1 in contrast to no or limited expression in squamous cell carcinoma of the esophagus, cervix, and oral cavity. The NACC1 expression profile is not significantly associated with the pathological parameters including the pT stage.
The present results suggest that NACC1 regulated by miR-331-3p contributes to cell proliferation and is a new potential target molecule for the diagnosis and treatment of UC.
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Nara Medical University.
Has not received any funding.
All authors have declared no conflicts of interest.