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  • Long non-coding RNA FAM66C is associated with clinical progression and promotes cell proliferation by inhibiting proteasome pathway in prostate cancer.

Long non-coding RNA FAM66C is associated with clinical progression and promotes cell proliferation by inhibiting proteasome pathway in prostate cancer.

Cell biochemistry and function (2020-05-21)
Yimin Xie, Jie Gu, Zhenqian Qin, Zhen Ren, Yanwei Wang, Haifeng Shi, Binghai Chen
RÉSUMÉ

Prostate cancer is the most prevalent malignancy in men, and the identification of novel oncogenes is clinically valuable for early screening, prevention and treatment. Recently, the studies have revealed that long non-coding RNAs (lncRNAs) play important roles in the development and progression of cancers including prostate cancer. The present study aims to identify a novel lncRNA that correlated with the survival time of prostate cancer patients and try to explore its biological functions in prostate cancer cells. After analysing the prostate carcinoma dataset of the Cancer Genome Atlas (TCGA), the lncRNA FAM66C was screened with its expression highly correlated with patient survival time, tumour stage and Gleason pattern. Real-time PCR showed that FAM66C highly expressed in prostate cancer cells, and knockdown FAM66C by siRNAs resulted in significant inhibition of cell growth. Furthermore, the results indicated that FAM66C promoted cell growth due to increasing cell proliferation but not decreasing cell apoptosis. In addition, FAM66C activated the epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinase (ERK) signalling to promote cell proliferation. The result of Western Blotting and lysosomal acidity detection showed that knockdown FAM66C increased the protein ubiquitination and the lysosomal acidity. Moreover, inhibition of proteasome pathway could increase the activation of EGFR-ERK signalling and cell proliferation. Taken together, these results suggested that lncRNA FAM66C activate EGFR-ERK signalling to promote cell proliferation by inhibiting proteasome pathway in prostate cancer. SIGNIFICANCE OF THE STUDY: We demonstrated that lncRNA FAM66C was associated with clinical progression. In addition, highly expressed lncRNA FAM66C in prostate cancer cell lines promoted cell proliferation. Moreover, lncRNA FAM66C activate the epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinase (ERK) signalling to promote cell proliferation by inhibiting proteasome pathway in prostate cancer. This study might provide lncRNA FAM66C as a potential therapeutic target gene of prostate cancer.

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