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Long non-coding RNA HOXA-AS3 facilitates the malignancy in colorectal cancer by miR-4319/SPNS2 axis.

Abstract
Growing evidence has shown the oncogenic role of long non-coding RNA HOXA-AS3 in the progression of several types of cancers, while the effect of HOXA-AS3 on colorectal cancer (CRC) remains unclear. In this study, HOXA-AS3 was significantly over-expressed in CRC clinical samples and human CRC cell lines (SW480, SW620, HCT116, COLO205, and LOVO). HOXA-AS3 knockdown was further achieved by specific siRNAs in COLO205 and LOVO cell lines. The depletion of HOXA-AS3 remarkably inhibited cell proliferation, induced cell cycle arrest, and promoted cell apoptosis in CRC cell lines. Additionally, HOXA-AS3 knockdown was determined to facilitate miR-4319 expression and reduce expression level of sphingolipid transporter 2 (SPNS2) in CRC cell lines. The dual luciferase reporter assay suggested that HOXA-AS3 acted as a sponge of miR-4319, and miR-4319 further directly targeted SPNS2 for expression regulation. Besides, HOXA-AS3 was determined to mediate CRC cell proliferation and apoptosis via miR-4319/SPNS2 axis. Moreover, tumorigenesis experiment validated that HOXA-AS3 promoted CRC progression in vivo by regulating miR-4319, SPNS2, and protein kinase B (AKT) signaling. In summary, this study reveals the novel role of HOXA-AS3 in pathogenesis of CRC and provides a candidate for CRC therapeutic target.
AuthorsYang Jiang, Xiao-Yu Yu, Hui-Xin Sun, Xin-Yue Gu, Jing-Shu Geng
JournalJournal of physiology and biochemistry (J Physiol Biochem) Vol. 77 Issue 4 Pg. 653-666 (Nov 2021) ISSN: 1877-8755 [Electronic] Spain
PMID34671931 (Publication Type: Journal Article)
Copyright© 2021. University of Navarra.
Chemical References
  • Anion Transport Proteins
  • MicroRNAs
  • RNA, Long Noncoding
  • Spns2 protein, human
Topics
  • Anion Transport Proteins
  • Carcinogenesis
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms (genetics)
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs (genetics)
  • RNA, Long Noncoding (genetics)

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