Down-regulation of MALAT1 inhibits cervical cancer cell invasion and metastasis by inhibition of epithelial–mesenchymal transition

Abstract

The metastasis-associated lung adenocarcinoma transcript 1(MALAT1), a member of the long non-coding RNA (lncRNA) family, has been reported to be highly enriched in many kinds of cancers and to be a metastasis marker and a prognostic factor. In this study, we found that MALAT1 expression levels were significantly increased in cervical cancer (CC) cells and tissues. The down-regulation of MALAT1 by shRNA in CC cells inhibited the invasion and metastasis in vitro and in vivo. Microarray analysis showed that the knockdown of MALAT1 up-regulated the epithelial markers E-cadherin and ZO-1, and down-regulated the mesenchymal markers β-catenin and Vimentin. This regulation was further confirmed by subsequent observation from RT-PCR, western blot, and immunofluorescence results. Meanwhile, the transcription factor snail, which functions to modulate epithelial-mesenchymal transition (EMT), was also down-regulated at both transcript and protein levels by MALAT1 down-regulation. In addition, we found that MALAT1 expression levels were positively related to HPV infection in cervical epithelial tissues by microarray analysis. Taken together, these results suggest that MALAT1 functions to promote cervical cancer invasion and metastasis via induction of EMT, and it may be a target for the prevention and therapy of cervical cancers.

Upregulated NNT-AS1, a long noncoding RNA, contributes to proliferation and migration of colorectal cancer cells in vitro and in vivo

“…HOX transcript antisense RNA (HOTAIR) was proved to promote EMT in cervical cancer [18]. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) has been shown to promote cell invasion and metastasis by inducting EMT in cervical cancer [19]. …”

Long Non-Coding RNAs: Key Regulators of Epithelial-Mesenchymal Transition, Tumour Drug Resistance and Cancer Stem Cells

“…MALAT-1 is overexpressed and has been linked to the promotion of EMT in bladder cancer, cervical cancer, NSCLC, pancreatic cancer and renal cell carcinoma [91,274,275,276,277,278,279]. However, contradictory results have been obtained for the effect of MALAT-1 on EMT in breast cancer cells, with two studies reporting the promotion of EMT by MALAT-1 [89,280] and another reporting inhibition of EMT by MALAT-1 [97].…”

Functions and regulatory mechanisms of metastasis‐associated lung adenocarcinoma transcript 1

“…As one of the first identified cancer‐associated lncRNAs, MALAT1 was reported to be overexpressed in gastric cancer (Chen, Liu, Wang et al, 2017), breast cancer (Arun et al, ), prostate cancer (Ren et al, ), cervical cancer (Sun, Qin et al, ), acute myeloid leukemia (Chen, Nagel et al, 2018), medullary thyroid cancer (Chu, Hardin, Schneider, Chen, & Lloyd, ), choriocarcinoma (Shi, Wang, & Yin, ), gallbladder cancer (Sun et al, ), pancreatic cancer (Xie et al, 2017), multiple myeloma (Liu, Wang et al, ), ovarian cancer (Wu et al, 2017), T and natural killer cell lymphoma (Kim, Kim, Yang, Kim, & Yoon, ), acute monocytic leukemia (Huang, Liu et al, ), endometrial stromal sarcoma (Yamada et al, ), myeloma (Cho et al, ), clear cell renal cell carcinoma (Zhang, Yang, Chen, Che, & Zheng, ), esophageal squamous cell carcinoma (Hu et al, ), glioma (Ma, Wang, Li et al, ), osteosarcoma (Cai et al, ), neuroblastoma (Tee et al, ), tongue squamous cell carcinomas (Fang et al, ), hilar cholangiocarcinoma (Tan, Huang, & Li, ), mantle cell lymphoma (Wang, Zhu et al, ), and other tumor tissues. It has been reported that MALAT1 is involved in the regulation of tumor proliferation, apoptosis, invasion, metastasis, and angiogenesis.…”

“…It is suggested that after binding to a specific protein, MALAT1 can shuttle between the cytoplasm and the nucleus to alter the intracellular localization of the protein. MiR-129-5p Growth and metastasis of triple-negative breast cell↑ Zuo, Li, Zhou, Ma, and Fu (2017) MiR-142-3p and miR-129-5p HMGB1 Growth of osteosarcoma cell↑ MiR-129-5p HMGB1 Proliferation of colon cancer↑ Jie and Zhao (2017) MiR-133 Srf Differentiation of myocyte↑ Han, Yang Cao, and Liang (2015) MiR-140 Slug and ADAM10 Growth and invasion of uveal melanoma cell↑ MiR-140 NFYA Blood-tumor barrier permeability↓ Ma et al (2016) MiR-143-3p ZEB1 Growth and invasion of hepatocellular carcinoma cell↑ MiR-144-3p ROCK1 and ROCK2 Metastasis and proliferation of osteosarcoma cell↑ MiR-145 TGFBR2 and SMAD3 TGF-β1-induced EMT↑ Xiang, Zhang, Tang, and Li (2017) MiR-145 Bnip3 Cardioprotective effects↑ Zhao et al (2016) MiR-146b-5p TRAF6 Growth and metastasis of hepatocellular carcinoma cell↑ MiR-146a LPS-induced acute kidney injury↑ Ding et al (2018) MiR-155 FBXW7 Cell viability in glioma cell↓ Cao et al (2016) MiR-183 ITGB1 Cell growth in melanoma cell↑ Sun, Qin et al (2016) MiR-195 EGFR Growth and metastasis of hepatocellular carcinoma cell↑ MiR-200c ZEB1 and ZEB2 Endometriosis↑…”