LncRNA RP11-551L14.4 suppresses breast cancer development by inhibiting the expression of miR-4472

PeerJ. 2022 Dec 6:10:e14482. doi: 10.7717/peerj.14482. eCollection 2022.

Abstract

Background: Previous studies have been reported that long non-coding RNA (lncRNA) can regulate the expression of genes which are involved in many important cellular processes The potential role of lncRNA RP11-551L14.4 in the development of breast cancer and the possible regulatory mechanisms was investigated.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to analyze RP11-551L14.4 expression in 36 paired breast cancer tissues and adjacent tissues. The expression of RP11-551L14.4 in multiple breast cancer cell lines was detected by qRT-PCR. Meanwhile, overexpression of RP11-551L14.4 models was established using lentivirus in BT474 and T47D breast cancer cells. Cell counting kit-8 (CCK-8), cell colony formation and cell cycle assays were performed to detect the effects of RP11-551L14.4 on the biological function of breast cancer cells. Besides, bioinformatics techniques, dual luciferase reporter gene assay and rescue experiments were used to investigate the potential mechanisms.

Results: RP11-551L14.4 expression was negatively associated with the advanced tumor stage. Breast cancer patients with low RP11-551L14.4 expression manifested a poorer prognosis. The results of qRT-PCR showed that RP11-551L14.4 expression in breast cancer tissues was significantly lower than in adjacent tissues. Meanwhile, overexpression of RP11-551L14.4 significantly decreased the cell proliferation and cell cycle. Bioinformatics technology showed that RP11-551L14.4 could complementarily bind to miR-4472. qRT-PCR results indicated that the expression levels of miR-4472 and RP11-551L14.4 in breast cancer were negatively correlated. Luciferase reporter gene assay showed that miR-4472 remarkably decreased the relative luciferase activity of the wild-type RP11-551L14.4 vector. miR-4472 is a direct target gene of RP11-551L14.4. miR-4472 levels were reduced, and repulsive guidance molecule A (RGMA) mRNA or protein levels were increased after overexpression of RP11-551L14.4 in the breast cancer cells. miR-4472 reversed the effects caused by RP11-551L14.4 in breast cancer cells.

Conclusion: RP11-551L14.4 expression was remarkably decreased in breast cancer tissues and cells. RP11-551L14.4 may inhibit the malignant progression of breast cancer by regulating miR-4472 expression.

Keywords: Breast cancer; Proliferation; RP11-551L14.4; miR-4472.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Female
  • Humans
  • MicroRNAs* / genetics
  • RNA, Long Noncoding* / genetics

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • MIRN4472-1 microRNA, human
  • MIRN4472-2 microRNA, human

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 81672536, 82173170), the Science and Technology Research Program of Chongqing Municipal Education Commission (No. KJZD-K202000405), the Innovation research group in Colleges and Universities Program of Chongqing Municipal Education Commission (No. CXQT20012) and the project of the top-notch talent cultivation program for the graduate students of Chongqing Medical University (No. BJRC201918). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.