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. 2022;19(1):548-559.
doi: 10.1080/15476286.2021.1992995. Epub 2021 Dec 31.

LINC00857 regulated by ZNF460 enhances the expression of CLDN12 by sponging miR-150-5p and recruiting SRSF1 for alternative splicing to promote epithelial-mesenchymal transformation of pancreatic adenocarcinoma cells

Yong Zhang  1 , Yuan Fang  1 , Lijie Ma  1 , Jing Xu  1 , Chentao Lv  1 , Li Deng  1 , Guanghui Zhu  1   2
Affiliations

LINC00857 regulated by ZNF460 enhances the expression of CLDN12 by sponging miR-150-5p and recruiting SRSF1 for alternative splicing to promote epithelial-mesenchymal transformation of pancreatic adenocarcinoma cells

Yong Zhang et al. RNA Biol. 2022.

Abstract

Recent research unveiled that LINC00857 plays a regulatory role in multiple human cancers, such as lung adenocarcinoma and gastric cancer. Nevertheless, the function of LINC00857 in pancreatic adenocarcinoma (PAAD) remains unclear. This study concentrates on LINC00857 to discuss the relevant molecular mechanism of this gene in PAAD. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot were implemented for measuring the expressions of RNAs and proteins. Wound healing and Transwell assays were used to assess cell migration and invasion, and fluorescent in situ hybridization (FISH) to locate LINC00857 in PAAD cells. Additionally, mechanism assays were conducted to validate the interaction between genes. Results indicated that LINC00857 was upregulated in PAAD cells and the knockdown of LINC00857 impeded PAAD cell migration, invasion and epithelial-mesenchymal transition (EMT). Further, it was found that LNC00857 regulates CLDN12 expression by targeting miR-150-5p. Moreover, LINC00857 was confirmed to recruit serine/arginine-rich splicing factor 1 (SRSF1) to promote the alternative splicing (AS) targeting CLDN12, affecting the phenotypes of PAAD cells. In addition, the transcription factor ZNF460 was proven to positively regulate LINC00857 expression. To sum up, LINC00857 regulated by ZNF460 upregulates CLDN12 expression by sponging miR-150-5p and recruiting SRSF1 to facilitate the progression of PAAD cells.[Figure: see text].

Keywords: CLDN12; LINC00857; SRSF1; alternative splicing; pancreatic adenocarcinoma; transcription factor.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
LINC00857 promotes malignant phenotypes of PAAD cells.
Figure 2.
Figure 2.
LINC00857 regulates the expression of CLDN12 by sponging miR-150-5p in PAAD cells.
Figure 3.
Figure 3.
CLDN12 facilitates the malignant phenotypes of PAAD cells.
Figure 4.
Figure 4.
LINC00857 recruits SRSF1 for alternative splicing to regulate CLDN12 expression in PAAD cells.
Figure 5.
Figure 5.
ZNF460 as the transcription factor of LINC00857 promoter regulates LINC00857 expression in PAAD cells.
None
See this image and copyright information in PMC

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