LncRNA—UCA1 enhances cell proliferation and 5-fluorouracil resistance in colorectal cancer by inhibiting miR-204-5p

Abstract

Recent preliminary studies reported the in vitro tumor-promoting effects of long non-coding RNA urothelial carcinoma associated 1 (UCA1) in colorectal cancer (CRC). However, the in vivo functions and molecular mechanism of UCA1 in CRC remain unclear. Therefore, we investigated the detailed role and mechanism of UCA1 in CRC. We found that UCA1 was up-regulated in CRCs and negatively correlated with survival time in two CRC cohorts. Functional assays revealed the in vitro and in vivo growth-promoting function of UCA1 and revealed that UCA1 can decrease the sensitivity of CRC cells to 5-FU by attenuating apoptosis. Further mechanistic studies revealed that UCA1 could sponge endogenous miR-204-5p and inhibit its activity. We also identified CREB1 as a new target of miR-204-5p. The protein levels of CREB1 were significantly up-regulated in CRCs, negatively associated with survival time and positively correlated with the UCA1 expression. The present work provides the first evidence of a UCA1-miR-204-5p-CREB1/BCL2/RAB22A regulatory network in CRC and reveals that UCA1 and CREB1 are potential new oncogenes and prognostic factors for CRC.

Long Noncoding RNA HOXA-AS2 Promotes Papillary Thyroid Cancer Progression by Regulating miR-520c-3p/S100A4 Pathway

“…LncRNAs (long noncoding RNAs) are broadly defined as noncoding RNA molecules longer than 200 nucleotides [20,21]. They are key elements in cell differentiation and ontogenetic process through interactions with DNA, chromatin, regulatory proteins and a variety of cellular RNA species.…”

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“…Uptake of exosomal UCA1 induced tamoxifen resistance in sensitive cancer cells (137). Even though the detailed mechanism was not revealed in this study, UCA1 was previously found to induce aggressive phenotype and drug resistance by suppression of p27 (138) or acting as sponge for miR-143 (139) and miR-204-5p (140). …”

Long Non-coding RNA Landscape in Colorectal Cancer

“…However, in one of the recent study, the presences of lncRNAs such as UCA1 and sNAR have been shown to affect the effectiveness of the 5-FU treatment. Downregulation of snaR could decrease the sensitivity towards 5-FU and drug-induced cell death in CRC cells whereas the upregulation of UCA1 in CRC reduces the sensitivity towards 5-FU and drug-induced cell death through inhibiting the activity of miR204-5p as a sponge [36,37] . Therefore, the complexity of lncRNA in the progression of cancer and its involvement in the treatment and diagnosis of cancer requires further research in order for greater understanding and its subsequent clinical translation.…”