Long noncoding RNA uc.338 promotes cell proliferation through association with BMI1 in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common human cancers all over the world. Increasing evidences have demonstrated that long noncoding RNAs (lncRNAs) play important roles in malignant transformation, tumor growth and metastasis in HCC. Among lncRNAs, ultraconserved RNAs (ucRNAs) containing an ultraconserved region have been report to contribute to human cancers. lncRNA ultraconserved element 338 (uc.338) was first found to be upregulated in HCC and promote cell growth. However, the exact mechanism by which uc.338 modulates cell growth remains unclear. In the present study, we demonstrated that uc.338 promotes HCC cell proliferation and induces cell cycle progression. RNA-immunoprecipitation and RNA pull-down assays showed that uc.338 associated with BMI1. We found that uc.338 promotes HCC cell proliferation and induces cell cycle progression through association with BMI1. uc.338 also modulated the transcription of CDKN1A. The oncogenic activity of uc.338 is partially due to its repression of p21. uc.338 may be a potential target for HCC therapy.

uc.338 targets p21 and cyclin D1 via PI3K/AKT pathway activation to promote cell proliferation in colorectal cancer

“…Previous studies have shown that uc.338 is involved in the progression of various tumors. For example, Bo et al found that uc.338 promoted HCC cell proliferation and induced cell cycle progression through an association with BMI1 in hepatocellular carcinoma (10). Gao et al found that uc.338 could promote proliferation and metastasis by cyclin B1 and EMT activation in lung carcinoma (13).…”

“…T-UCRs have been reported to be involved in various cancer processes (5)(6)(7)(8)(9). As a member of the T-UCR family, uc.338 has been reported to promote tumorigenesis in hepatocellular carcinoma (9)(10)(11), cervical cancer (12) and lung carcinoma (13). In CRC, uc.338 was reported to promote the invasion and metastasis of HCT116 and SW480 cells (14).…”

Dysregulated long noncoding RNAs (lncRNAs) in hepatocellular carcinoma: implications for tumorigenesis, disease progression, and liver cancer stem cells

“…lncRNAs may perform their biological functions via interacting with other proteins. For example, overexpression of a lncRNA termed ultraconserved element 338 (uc.338) was shown to promote the proliferation of HCC cells in a BMI1-dependent manner as confirmed by RNA pull down and RNA immunoprecipitation assays [ 54 ].…”

Highlighting transcribed ultraconserved regions in human diseases

“…Different pathways in the regulation of uc.338 that lead to inhibition of p21 are proposed: (a) binding of p21 to polycomb complex 1, more specifically to BMI1, which suppresses p21 (Bo, Li, Li, Liang, & An, ); (b) promotion of p21 downregulation and cyclin D1 upregulation via the PI3K/AKT pathway in CRC cells (Y. Zhang et al, ); and (c) negative regulation of TIMP‐1 expression, which is a natural inhibitor of the matrix metalloproteinase, and also contributes to cell proliferation and migration in CRC (C. Wang et al, ). Furthermore, uc.338 is associated with larger tumors, deeper tumor invasion, increased lymph node metastasis in CRC, and poorer prognosis in CRC and NSCLC (Tian & Feng, ).…”