1. Hypoxia activated long non-coding RNA HABON regulates the growth and proliferation of hepatocarcinoma cells by binding to and antagonizing HIF-1 alpha.
- Author
-
Ma CN, Wo LL, Wang DF, Zhou CX, Li JC, Zhang X, Gong XF, Wang CL, He M, and Zhao Q
- Subjects
- Apoptosis, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular metabolism, Cell Communication, Cell Proliferation, Humans, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Liver Neoplasms genetics, Liver Neoplasms metabolism, Tumor Cells, Cultured, Tumor Microenvironment, Carcinoma, Hepatocellular pathology, Gene Expression Regulation, Neoplastic, Hypoxia physiopathology, Hypoxia-Inducible Factor 1, alpha Subunit antagonists & inhibitors, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Liver Neoplasms pathology, RNA, Long Noncoding genetics
- Abstract
The adaptation of tumour cells to hypoxic microenvironment is one of the most significant characteristics of many malignant tumour diseases including hepatocarcinoma. Recently, long non-coding RNAs (lncRNAs) have been reported to play important roles in the various levels of gene regulation thus functioning in growth and survival of tumour cells. Here, new hypoxia-related lncRNAs in hepatocarcinoma cells were screened and validated by lncRNA chip-array as well as real-time RT-PCR. Among them, a hypoxia-activated lncRNA that we identified and termed Hypoxia-Activated BNIP3 Overlapping Non-coding RNA (HABON), was not only regulated by hypoxic-induced factor-1α (HIF-1α) but its expression increased significantly under hypoxia in tumour cells. We deciphered the biological characteristics of HABON including its cell localization, genomic location, as well as its full-length sequence, and proved HABON could promote growth, proliferation and clone-formation of hepatocarcinoma cells under hypoxia. Then, we revealed that HABON was transcriptionally activated by HIF-1α in hypoxic cells, furthermore, it could interact with HIF-1α and promote its protein degradation, thus affecting transcription of HIF-1α's target genes to exert its effects on cells. Besides, the elevated expression of HABON under hypoxia could promote the transcriptional activation of BNIP3 through HIF-1α, and increasing the expression level of BNIP3. This research provides a novel clue for the adaptive survival and growth mechanism of tumour under hypoxia, and gives a way to reveal the nature of tumour cells' resistance characteristics to harsh microenvironment.
- Published
- 2021
- Full Text
- View/download PDF