Abstract
Several studies have indicated that dysregulation of long non‑coding RNAs (lncRNAs) participates in the initiation and progression of cancer. The lncRNA MIR4435‑2HG was previously reported to act as an oncogene in human cancer, including liver cancer. However, its role in the pathogenesis in liver cancer is largely unclear. The present study aimed to reveal the molecular mechanism by which MIR4435‑2HG regulates liver cancer. The expression levels of MIR4435‑2HG in liver cancer and adjacent normal tissues were analyzed using The Cancer Genome Atlas database. MIR4435‑2HG expression was validated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) in cancer cells in vitro. The target genes of MIR4435‑2HG were predicted using bioinformatics analysis. Interactions between miR‑136‑5p, MIR4435‑2HG and B3GNT5 were detected using luciferase reporter assays, and their effects on cell viability, migration and invasion were assessed using Cell Counting Kit‑8, wound healing and Transwell assays. The effects of miR‑136‑5p and MIR4435‑2HG on B3GNT5 expression were confirmed by western blot analysis. The results revealed that MIR4435‑2HG expression was upregulated in primary liver cancer and liver cancer cell lines, and was positively associated with advanced tumor stage, metastasis and poor prognosis in patients with liver cancer. Knockdown of MIR4435‑2HG significantly inhibited the proliferation, migration and invasion of liver cancer cells. Furthermore, miR‑136‑5p was determined to be a direct target of MIR4435‑2HG and suppressed MIR4435‑2HG expression by binding with the seed region of the 3'‑UTR of MIR4435‑2HG in liver cancer cells. Functional studies showed that the inhibitory effects of MIR4435‑2HG knockdown on cell proliferation, migration and invasion were significantly rescued by inhibiting miR‑136‑5p. Furthermore, the target gene, B3GNT5, of miR‑136‑5p was confirmed by bioinformatics analysis and RT‑qPCR. In addition, B3GNT5 expression was regulated by the MIR4435‑2HG/miR‑136‑5p axis. In conclusion, the present study indicated that MIR4435‑2HG facilitated the progression of liver cancer via the MIR4435‑2HG/miR‑136‑5p/B3GNT5 axis, which demonstrated that MIR4435‑2HG may be a potential biomarker for the prognosis and treatment of liver cancer.
Keywords
B3GNT5
MIR4435‑2HG
liver cancer
microRNA‑136‑5p
proliferation
MeSH Terms
Apoptosis
Biomarkers, Tumor/genetics,metabolism
Cell Proliferation
Female
Gene Expression Regulation, Neoplastic
Glycosyltransferases/genetics,metabolism
Humans
Liver Neoplasms/genetics,metabolism,pathology
Male
MicroRNAs/genetics
Middle Aged
Prognosis
RNA, Long Noncoding/genetics
Survival Rate
Tumor Cells, Cultured
Chemicals
Biomarkers, Tumor
MIR4435-2HG long non-coding RNA, human
MIRN136 microRNA, human
MicroRNAs
RNA, Long Noncoding
B3GNT5 protein, human
Glycosyltransferases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Zhu Yungang
Radiology Department, Tianjin Teda Hospital, Tianjin 300457, P.R. China.
Li Baoguo
Department of Interventional Treatment, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China.
Xu Guoping
Medical Imaging Department, Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.
Han Changrui
Radiology Department, Tianjin Teda Hospital, Tianjin 300457, P.R. China.
Xing Gang
Radiology Department, Tianjin Teda Hospital, Tianjin 300457, P.R. China.
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