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KMID : 0381120220440121577
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Genes and Genomics
2022 Volume.44 No. 12 p.1577 ~ p.1591
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Long non-coding RNA H19X promotes tumorigenesis and metastasis of colorectal cancer through regulating the miR-503-5p/KANK1 axis
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Yuan Zihan
Zhao Haizhou
Zhi Qiaoming
Wang Sentai
Liu Chao
Han Ye
Xu Zhihua
Liu Fei
Liu Xingyi
Zan Xinquan
Wang Qiang
Wan Daiwei
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Abstract
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Background: It has been well established that the long non-coding RNAs (lncRNAs) plays a critical role in tumor progression. However, the function of these transcripts and mechanisms responsible for their deregulation in colorectal cancer (CRC) remain to be investigated.
Objective: To explore the potential effect and regulation mechanism of lncRNA H19X in colorectal cancer.
Methods: We predicted and validated long non-coding RNA H19X from microarray data of colorectal cancer tissues. In addition, the biological behaviors of H19X and miR-503-5p on CRC were examined in vitro and in vivo, including MTT, colony formation assay, Hoechst33342 and transwell assay. The mRNA and protein levels of KN Motif and Ankyrin Repeat Domains 1 (KANK1) were analyzed by Quantitative real-time PCR (qRT-PCR), western blotting (WB) assay. Moreover, bioinformatics tools and dual-luciferase reporter assay were applied to demonstrate the relationship between KANK1 and miR-503-5p.
Results: H19X was remarkably up-regulated in CRC tissues. Its expression related to tumor size (p = 0.041), lymph node metastasis (p = 0.037), distal metastasis (p = 0.028), advanced TNM stage (p = 0.034) and poor survival in CRC. H19X acted as an oncogenic lncRNA that induced CRC cell proliferation, invasion and metastasis. Through a number of functional studies, we found that H19X silencing inhibited the malignance phenotype of cancer cells through loss of miR-503-5p. Further studies demonstrated that miR-503-5p was involved in the progression of CRC by directly regulating the downstream target KANK1.
Conclusion: Collectively, the findings of the present study indicate H19X/miR-503-5p/KANK1 axis has critical role in the progression of colorectal cancer, providing an effective prognostic indicator and promising target in treatment of colorectal cancer.
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KEYWORD
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Colorectal cancer, Invasion, Proliferation, lncRNA, miRNA.
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