Long ncRNA MALAT1 promotes cell proliferation, migration, and invasion in prostate cancer via sponging miR-145

Dingrong Zhang; Cheng Fang; Haibo Li; Chunyuan Lu; Jiaohong Huang; Jiancheng Pan; Zhizhao Yang; Enli Liang; Zhifei Liu; Xiaodong Zhou; Zhongcheng Xin; Yegang Chen; Qiliang Cai

doi:10.21037/tau-20-1526

Long ncRNA MALAT1 promotes cell proliferation, migration, and invasion in prostate cancer via sponging miR-145

Transl Androl Urol. 2021 Jun;10(6):2307-2319. doi: 10.21037/tau-20-1526.

Authors

Dingrong Zhang¹, Cheng Fang¹, Haibo Li², Chunyuan Lu³, Jiaohong Huang⁴, Jiancheng Pan¹, Zhizhao Yang¹, Enli Liang¹, Zhifei Liu⁵, Xiaodong Zhou¹, Zhongcheng Xin^{1

6}, Yegang Chen¹, Qiliang Cai¹

Affiliations

¹ Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
² Department of Urology, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Tianjin, China.
³ Department of Anesthesia, the Second hospital of Tianjin Medical University, Tianjin, China.
⁴ Department of Geriatric, the Second Hospital of Tianjin Medical University, Tianjin, China.
⁵ Department of Urology, Tangshan People's Hospital, Tangshan, China.
⁶ Andrology Center, Peking University First Hospital, Peking University, Beijing, China.

Abstract

Background: The long non-coding (lncRNA) RNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is known to promote tumorigenesis, whereas microRNA-145 (miR-145) plays an antitumor role in several cancers. In this study, we aimed to elucidate the role of MALAT1 and miR-145 in prostate cancer cells and investigate the effect of MALAT1 downregulation on prostate cancer (PCa) cells in vitro in vivo.

Methods: The Cancer Genome Atlas (TCGA) datasets were used to carry out the initial bioinformatics analysis; the findings were then tested in LNCaP and CWR22Rv1 cell lines. Western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to evaluate the levels of MALAT1 and miR-145 along with related biomarkers. Furthermore, wound-healing and Transwell assays were performed to test the migratory and invasive abilities of PCa cells. Luciferase reporter assays were used to validate the relationship between MALAT1 and miR-145; their down-stream target genes were also studied. To further substantiate these findings in an animal model, tumor studies including immunofluorescence staining of tissues were carried in nude mice.

Results: The expression of MALAT1 was upregulated in both LNCaP cell lines and CWR22Rv1 cell lines (F=2.882, t=13.370, P<0.001; F=2.268, t=15.859, P<0.001). Knockdown of MALAT1 reduced the migratory and invasive capabilities of PCa cells (F=0.017, t=12.212, P<0.001; F=10.723, t=6.016, P=0.002). Using direct binding, MALAT1 suppressed the antitumor function of miR-145, which in turn upregulated transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) via SMAD3 and TGFBR2 (F=2.097, t=5.389, P=0.006; F=1.306, t=4.155, P=0.014).

Conclusions: We confirmed that MALAT1 acts as a competing endogenous RNA (ceRNA) of miR-145. The MALAT1 based regulation of MiR-145-5p-SMAD3/TGFBR2 interactions could be an intriguing molecular pathway for the progression of PCa.

Keywords: MALAT1; epithelial-mesenchymal transition (EMT); miR-145; prostate cancer.