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THUMPD3-AS1 facilitates cell growth and aggressiveness by the miR-218-5p/SKAP1 axis in colorectal cancer

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A Correction to this article was published on 27 November 2023

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Abstract

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.

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Abbreviations

CRC:

colorectal cancer

COAD:

colon adenocarcinoma

SKAP1:

Src kinase associated phosphoprotein 1

THUMPD3-AS1:

THUMPD3 antisense RNA 1, miR-218-5p, microRNA-218-5p

ceRNA:

competing endogenous RNA

RT-qPCR:

reverse transcription quantitative polymerase chain reaction

ncRNA:

noncoding RNA

DFS:

disease free survival

OS:

overall survival

DMEM:

Dulbecco’s Modified Eagle Medium

FBS:

fetal bovine serum

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

Wt:

wild type

Mut:

mutant type

NC:

negative control

GAPDH:

glyceraldehyde-3phosphate dehydrogenase.

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  1. These authors contributed equally: Yuwei Pu, Jinrong Wei

Authors and Affiliations

  1. Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, China

    Yuwei Pu, Jinrong Wei, Yong Wu, Kui Zhao, Yongyou Wu, Shu Wu, Xiaodong Yang & Chungen Xing

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  1. Yuwei Pu
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Pu, Y., Wei, J., Wu, Y. et al. THUMPD3-AS1 facilitates cell growth and aggressiveness by the miR-218-5p/SKAP1 axis in colorectal cancer. Cell Biochem Biophys 80, 483–494 (2022). https://doi.org/10.1007/s12013-022-01074-4

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