LncRNA TP73-AS1 Promotes Cell Proliferation and Inhibits Cell Apoptosis in Clear Cell Renal Cell Carcinoma Through Repressing KISS1 Expression and Inactivation of PI3K/Akt/mTOR Signaling Pathway.
Liu. Guanghua G; Zhao. Xin X; Zhou. Jingmin J; Cheng. Xiangming X; Ye. Zixing Z; Ji. Zhigang Z
Key Findings
- TP73‑AS1 is over‑expressed in clear cell renal cell carcinoma and correlates with worse prognosis.
- TP73‑AS1 suppresses the tumor‑suppressor gene KISS1 by recruiting EZH2 to its promoter.
- Knocking down TP73‑AS1 restores KISS1 expression, reduces cancer cell proliferation and invasion, and triggers apoptosis.
- TP73‑AS1 influences the PI3K/Akt/mTOR signaling pathway, linking it to cell growth control.
Practical Outcomes
- For the biohacker community, this study does not provide an actionable supplement or protocol. It suggests that future therapies might aim to block TP73‑AS1 or boost KISS1/kisspeptin activity, but such approaches are still experimental and not ready for self‑use.
Summary
Scientists discovered that a non‑coding RNA called TP73‑AS1 is higher in kidney cancer tissue and helps the cancer grow by turning off the KISS1 gene, which normally makes a protein (kisspeptin) that can suppress tumors. When they lowered TP73‑AS1 in lab cells, KISS1 levels went up, cancer cell growth slowed, and more cells died. This work is about cancer biology, not a direct health‑boosting tip for everyday people.
Abstract
Emerging evidence suggests that long non-coding RNAs (lncRNAs) play a vital regulatory role in the pathogenesis and progression of renal cell carcinoma (RCC). We aim to determine lncRNA profiles in clear cell RCC (ccRCC) and investigate key lncRNAs involved in ccRCC tumorigenesis and progression. RNA sequencing technique and qPCR were used to determine the candidate lncRNAs in ccRCC tissues. The correlations between lncRNA P73 antisense RNA 1T (TP73-AS1) levels and survival outcomes were analyzed to elucidate its clinical significance. The underlying mechanisms of TP73-AS1 in ccRCC were analyzed through in vitro functional assays. We found TP73-AS1 was upregulated in 40 ccRCC tissues compared with adjacent normal renal tissues and increased TP73-AS1 was correlated to aggressive clinicopathologic features and unfavorable prognosis. Knockdown of TP73-AS1 suppressed cell proliferation, invasion and induced cell apoptosis. We also identified KISS-1 metastasis-suppressor (KISS1) was significantly upregulated in TP73-AS1 knockdown cells. Further, we revealed that TP73-AS1 suppressed KISS1 expression through the interaction with Enhancer of zeste homolog 2 (EZH2) and the specific binding to KISS1 gene promoter region. Knockdown of KISS1 partly reversed TP73-AS1 knockdown-induced inhibition of cell proliferation and promotion of apoptosis. We further determined that TP73-AS1 knockdown activated PI3K/Akt/mTOR signaling pathway, while overexpression of TP73-AS1 induced inhibition of PI3K/Akt/mTOR pathway and these effects could be partly abolished by overexpression of KISS1. In conclusion, we identified that TP73-AS1 as an oncogenic lncRNA in the development of ccRCC and a potential target for human renal carcinoma treatment.
Study Information
pubmed
2018
2018-07-17T00:00:00.000Z
10.1159/000491767
58
40