Long noncoding RNA kcna3 inhibits the progression of colorectal carcinoma through down-regulating YAP1 expression
Xiaolin Zhong1, Muhan Lü2, Juyi Wan2
1The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Abstract:
Long non-coding RNAs (lncRNAs) regulate diverse cellular processes, and their anomalous expression exert an essential role in the progression of many kinds of cancers, including colorectal carcinoma (CRC). The objective of this study was to investigate the role of lncRNA kcna3 and its underlying mechanism in CRC progression. The expression of lncRNA kcna3 in human CRC tissues and the adjacent non-tumor tissues was evaluated by RT-PCR. The correlations between lncRNA kcna3 expression levels and the overall survival (OS), as well as the clinicopathological features of CRC patients were analyzed. Gain-of-function and loss-of-function experiments were used to evaluate the effects of lncRNA kcna3 on the proliferation, apoptosis, migration, invasion and tumorigenesis of colon cancer SW620 cells. We found that lncRNA kcna3 was lowly expressed in CRC tissues, and its low expression was closely associated with patients' higher TNM grade and the higher occurrence rate of lymphatic metastasis and distant metastasis, as well as shorter OS. Enhanced expression of lncRNA kcna3 inhibited SW620 cells' proliferation, migration and invasion, and induced cell apoptosis in vitro, and repressed CRC tumor growth in vivo. Whereas knockdown of lncRNA kcna3 showed the opposite results. Mechanistically, up-regulation of lncRNA kcna3 decreased YAP1 protein expression and accelerated its degradation. The effects of lncRNA kcna3 overexpression on cell growth and tumorigenesis inhibition and apoptosis promotion were weakened when the expression of YAP1 was up-regulated. In conclusion, this study revealed that lncRNA kcna3 exerts a tumor-inhibit role in CRC progression through down-regulating YAP1 expression, indicating that lncRNA kcna3/YAP1 might be served as a new prognostic biomarker and therapeutic target for CRC.
Insights
Long non-coding RNA kcna3 is downregulated in colorectal cancer (CRC), suppressing tumor growth and metastasis. Its low expression correlates with poor patient survival, suggesting kcna3 as a potential therapeutic target for CRC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Long non-coding RNAs (lncRNAs) are crucial regulators of cellular functions.
- Aberrant lncRNA expression is implicated in cancer development, including colorectal carcinoma (CRC).
- The specific role of lncRNA kcna3 in CRC progression requires elucidation.
Purpose of the Study:
- To investigate the role and mechanism of lncRNA kcna3 in colorectal cancer.
- To assess the correlation between lncRNA kcna3 expression and CRC patient outcomes.
- To explore lncRNA kcna3's potential as a prognostic biomarker and therapeutic target.
Main Methods:
- RT-PCR was used to evaluate lncRNA kcna3 expression in CRC tissues versus adjacent non-tumor tissues.
- Correlation analyses were performed between lncRNA kcna3 levels and clinicopathological features, including overall survival.
- In vitro (SW620 cells) and in vivo gain-of-function and loss-of-function experiments assessed kcna3's impact on CRC cell behavior and tumor growth.
Main Results:
- lncRNA kcna3 was significantly downregulated in CRC tissues.
- Low kcna3 expression correlated with advanced TNM stage, increased lymphatic and distant metastasis, and shorter overall survival.
- Overexpression of kcna3 inhibited CRC cell proliferation, migration, and invasion, while promoting apoptosis in vitro and repressing tumor growth in vivo.
- Knockdown of kcna3 yielded opposite effects.
- Mechanistically, kcna3 overexpression reduced YAP1 protein levels and accelerated its degradation.
Conclusions:
- lncRNA kcna3 functions as a tumor suppressor in colorectal cancer.
- The tumor-inhibitory role of kcna3 is mediated by downregulating YAP1 expression.
- lncRNA kcna3 and its interaction with YAP1 represent promising prognostic biomarkers and therapeutic targets for CRC.
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