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

Abstract

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

Long noncoding RNA FAM66C promotes tumor progression and glycolysis in intrahepatic cholangiocarcinoma by regulating hsa‐miR‐23b‐3p/KCND2 axis

“…LncRNAs and miRNAs have also been found to play a regulatory role in the growth, metastasis and progression of ICC, such as lncRNA MNX1‐AS1, 14 lncRNA CCAT1, 15 and lncRNA SNHG3 16 . The previous study showed that lncRNA FAM66C promotes proliferation via the inhibition of the proteasomal pathway in prostate cancer 17 . The lncRNA FAM66C (hereinafter referred to as FAM66C, Gene ID: HSALNG0089050) is located on chromosome 12 with 46 243 nucleotides.…”

Stage-Specific Non-Coding RNA Expression Patterns during In Vitro Human B Cell Differentiation into Antibody Secreting Plasma Cells

“…FAM66C decreased expression following activation may be linked to the need for antibody secreting cells to have an active and functioning proteasome pathway to remove excess unfolded Ig molecules. Thus, this ncRNA has been shown to be associated with inhibiting the proteasome pathway in prostate cancer [59]. The lncRNA MATN1-AS1 has been shown to inhibit proliferation in the context of glioblastoma due to its ability to inhibit expression of RELA [60].…”

LncRNA-FAM66C Was Identified as a Key Regulator for Modulating Tumor Microenvironment and Hypoxia-Related Pathways in Glioblastoma

“…MIR210HG is also identified as a prognostic lncRNA in glioma ( 60 ), hepatocellular carcinoma ( 61 ), and colorectal adenocarcinoma ( 62 ). FAM66C is not much reported compared to the above lncRNAs, but it is illustrated to promote cell proliferation by suppressing proteasome pathway in prostate cancer, promote cancer progression in cholangiocarcinoma and pancreatic cancer ( 63 – 65 ). MYCNOS also functions as an oncogenic role in promoting GBM cell proliferation and hepatocellular carcinoma invasion ( 66 , 67 ).…”