Long non-coding RNA H19X promotes tumorigenesis and metastasis of colorectal cancer through regulating the miR-503-5p/KANK1 axis.

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.