LINC00346 Acts as a Competing Endogenous RNA Regulating Development of Hepatocellular Carcinoma via Modulating CDK1/CCNB1 Axis

Abstract

Hepatocellular carcinoma (HCC) is one of the important types of liver cancer. LncRNA is an important regulatory factor that regulates many biological processes such as tumor cells during tumorigenesis and metastasis. LINC00346 has been associated with various types of liver cancer, but its role and regulatory mechanism in HCC remain unclear. In our study, we found the LINC00356-miR-199a-3p-CDK1/CCNB1 axis through bioinformatics analysis. The expressions of LINC00356, miR-199a-3p, CDK1, and CCNB1 in HCC and normal hepatocytes were determined by qRT-PCR and WB. The results showed that LINC00356, CDK1 and CCNB1 were highly expressed in HCC, while miR-199a-3p was lowly expressed. Dual luciferase reporter gene assay, RIP and RNA-pull down assays demonstrated the targeted binding relationship of LINC00346-miR-199a-3p-CDK1/CCNB1. Overexpressing LINC00460 and silencing miR-199a-3p promoted cell invasion, inhibited apoptosis of HCC, and arrested the cell cycle in S phase while opposite results were obtained when silencing LINC00346, CDK1, and CCNB1. LINC00346 indirectly affects liver cancer by promoting the expression of CDK1/CCNB1 through competitive adsorption of miR-199a-3p. In addition, the study also demonstrated that overexpression of LINC00346 indirectly inhibited the expression of p53 and p21 proteins by promoting CDK1/CCNB1 expressions, thereby blocking the p53 signaling pathway. These results proved that LINC00346 could regulate the expression of CDK1/CCNB1 through the competitive adsorption of miR-199a-3p, thereby affecting the p53 signaling pathway and finally regulating the apoptosis, invasion and cell cycle of HCC cells. In conclusion, LINC00346 can be used as a tumor promoter and potential therapeutic target for HCC metastasis and prognosis.

<p>CCNB1 Expedites the Progression of Cervical Squamous Cell Carcinoma via the Regulation by FOXM1</p>

“…Moreover, we proposed that FOXM1 directly bound to CCNB1 and recruited CBP/P300 to enhance the H3K27ac levels. Previous studies identified the oncogenic role of CCNB1 in different cancers, including hepatocellular carcinoma 15 and cervical cancer. 18 Also, CCNB1 represents a prognostic factor for overall survival and metastasis-free survival in breast cancer.…”

Long non‑coding RNA MKLN1‑AS aggravates hepatocellular carcinoma progression by functioning as a molecular sponge for miR‑654‑3p, thereby promoting hepatoma‑derived growth factor expression

“…Numerous lncRNAs, such as ubiquitin conjugating enzyme E2 R2-AS1 ( 34 ), colorectal neoplasia differentially expressed ( 35 ) and snail family transcriptional repressor 3-AS1 ( 36 ), are differentially expressed in HCC and are closely associated with clinicopathological factors and prognosis of patients with HCC ( 37 – 39 ). For instance, these lncRNAs participate in the regulation of various aggressive cellular features during hepatocarcinogenesis and cancer progression ( 40 – 42 ). Hence, identifying HCC-relevant lncRNAs, as well as understanding their detailed roles are critical for developing effective targets for the diagnosis, prognosis and therapy of HCC.…”

Bioinformatic Identification and Validation of Key Genes and Biological Pathways Involved in Hepatitis B Virus-related Hepatocellular Carcinoma

“…Zou Y, et al conducted a multi-omics analysis of CDK1, CCNB1 and CCNB2 and found that they are potential prognostic biomarkers and associated with immune cell in ltration in HCC [37]. The experimental version of the Jin J L, et al study con rmed LINC00346 could regulate LINC00346-miR-199a-3p-CDK1/CCNB1 Axis to in uence the progress of HCC [38]. CDC20, also known as cell division cycle 20, is an cell-cycle regulator required for the completion of mitosis and an activator of the anaphase-promoting complex/cyclostome (APC/C) in the cell cycle [39].…”