Long non‑coding RNA UCA1 promotes papillary thyroid cancer cell proliferation via miR‑204‑mediated BRD4 activation

Abstract

Long non‑coding RNA (lncRNA) urothelial carcinoma‑associated 1 (UCA1) has been used in tumor development and progression in many types of cancer. However, the function and mechanism underlying the action of UCA1 in papillary thyroid cancer (PTC) remains unclear. Therefore, these topics were investigated in the present study by in vitro and in vivo experiments. It was demonstrated that the expression level of UCA1 was more significantly upregulated in PTC cell lines and tissues when compared with the immortal human thyroid follicular cell line and adjacent normal tissues, respectively. UCA1 knockdown significantly inhibited PTC cell viability, colony formation and the bromodomain containing 4 (BRD4) expression level in vitro, and retarded PTC tumor growth in vivo. In the previous study, microRNA (miR)‑204 inhibited thyroid cancer progression and was regulated by UCA1 in other types of cancer. In addition, by conducting dual luciferase reporter assays, it was confirmed that miR‑204 directly binds to UCA1 and the 3'‑untranslated region of BRD4. Furthermore, UCA1 competed with BRD4 for miR‑204 binding. miR‑204 knockdown enhanced BRD4 expression, which can be partially restored by short hairpin‑UCA1. The results of the present study illustrated that UCA1 promotes PTC progression by acting as a competing endogenous RNA by sponging miR‑204. In conclusion, UCA1 may be regarded as an oncogenic lncRNA, promoting PTC cell proliferation, and be a potential target for human PTC treatment.

<p>Correlations of lncRNAs with cervical lymph node metastasis and prognosis of papillary thyroid carcinoma</p>

“…32 Two other studies also indicated the role of UCA1 in stimulating proliferation of PTC cells. 33,34 In line with these previous studies, we found that UCA1 was upregulated in PTC tissues and associated with prognosis by public data investigation. To further explore the clinical significance of UCA1 in PTC, qRT-PCR analysis was performed to determine UCA1 expression levels in PTC tissue, adjacent noncancerous control tissues, and metastatic cervical lymph nodes.…”

Crosstalk between the lncRNA UCA1 and microRNAs in cancer

“…It was found that UCA1 significantly promoted proliferation and migration of thyroid cancer cells; the underlying mechanism was that UCA1 competed with c-myc proto-oncogene (c-myc) for miR-135a binding [84]. Similarly, UCA1 promoted growth and invasion of papillary thyroid carcinoma by competing with bromodomain containing 4 (BRD4) or insulin-like growth factor-binding protein 5 (IGFBP5) for miR-204 binding [85,86].…”

Genome‐wide identification of a competing endogenous RNA network in cholangiocarcinoma

“…Among these lncRNAs involving in the ceRNA network, Li et al have reported that Linc00483 acting as ceRNA regulated proliferation and apoptosis via activating mitogen‐activated protein kinases in gastric cancer. In addition, recent studies indicated that lncRNA UCA1 played important roles in the progression of various cancers, including papillary thyroid carcinoma, melanoma, esophageal squamous cell carcinoma, and breast cancer . In the previous study, HULC could act as an oncogene through negatively regulating miR‐125a‐3p in ovarian carcinoma .…”

“…In addition, recent studies indicated that lncRNA UCA1 played important roles in the progression of various cancers, including papillary thyroid carcinoma, melanoma, esophageal squamous cell carcinoma, and breast cancer. [38][39][40][41] In the previous study, HULC could act as an oncogene through negatively regulating miR-125a-3p in ovarian carcinoma. 42 Importantly, lncRNA HULC, which was activated by oxidative stress, could enhance CCA cellular migration and invasion by a ceRNA mechanism.…”