Background: Colorectal cancer (CRC) is a malignant cancer with a high mortality. Accumulating studies have revealed that mRNAs involved in ceRNA (competing endogenous RNA) network are implicated in the tumorigenesis and development of CRC. Here, we aimed to elucidate the ceRNA network involving Src kinase associated phosphoprotein 1 (SKAP1) in the biological characteristics of CRC.
Methods: Expression levels of genes in colon adenocarcinoma (COAD) samples and prognosis of COAD patients were predicted using publicly available online tool. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), clony formation and Transwell assays were conducted to test the biological functions of SKAP1 and THUMPD3 antisense RNA 1 (THUMPD3-AS1) in CRC cells. Western blot was used to measure the protein levels of SKAP1. Gene expression in CRC cells was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The interaction between miR-218-5p and THUMPD3-AS1 (or SKAP1) was verified by RNA pulldown and luciferase reporter assays.
Results: SKAP1 was upregulated in COAD tissues and CRC cells and it reflected a poor prognosis in patients with COAD. SKAP1 knockdown inhibited CRC (HT-29 and HCT-116) cell proliferation, migration and invasion. Mechanistically, THUMPD3-AS1 acted as a ceRNA to sponge miR-218-5p and subsequently upregulated SKAP1 expression in CRC cells. SKAP1 overexpression reversed the suppressive effect of THUMPD3-AS1 knockdown on proliferation, migration and invision of CRC cells.
Conclusions: THUMPD3-AS1 promotes CRC cell growth and aggressiveness by regulating the miR-218-5p/SKAP1 axis.
Keywords: Colorectal cancer; SKAP1; THUMPD3-AS1; miR-218-5p.
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.