MiR-30c suppresses the proliferation, metastasis and polarity reversal of tumor cell clusters by targeting MTDH in invasive micropapillary carcinoma of the breast

Author(s): Yunwei Han ^a ^, ^b ^, ^c ^, ^d ^, ^e ^, ^f ^, ¹ , Weidong Li ^a ^, ^b ^, ^c ^, ^d ^, ^e ^, ^f ^, ¹ , Renyong zhi ^a ^, ^b ^, ^c ^, ^d ^, ^e ^, ^f , Gui Ma ^g ^, ^h ^, ⁱ , Ang Gao ^g ^, ^h ^, ⁱ , Kailiang Wu ^a ^, ^b ^, ^c ^, ^d ^, ^e ^, ^f , Hui Sun ^a ^, ^b ^, ^c ^, ^d ^, ^e ^, ^f , Dan Zhao ^g ^, ^h ^, ⁱ , Yiling Yang ^a ^, ^b ^, ^c ^, ^d ^, ^e ^, ^f , Fangfang Liu ^a ^, ^b ^, ^c ^, ^d ^, ^e ^, ^f , Feng Gu ^a ^, ^b ^, ^c ^, ^d ^, ^e ^, ^f , Xiaojing Guo ^a ^, ^b ^, ^c ^, ^d ^, ^e ^, ^f , Jintang Dong ^g ^, ^h ^, ⁱ , Shuai Li ^a ^, ^b ^, ^c ^, ^d ^, ^e ^, ^f ^, ^** , Li Fu ^a ^, ^b ^, ^c ^, ^d ^, ^e ^, ^f ^, ^j ^, ^k ^, ^l ^, ^*

Publication date (Electronic): 02 July 2024

Journal: Heliyon

Publisher: Elsevier

Keywords: Breast cancer, Invasive micropapillary carcinoma (IMPC), MiRNA, Proliferation, Metastasis, Polarity reversal

Read this article at

ScienceOpen Publisher PMC

Bookmark

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Purpose

Invasive micropapillary carcinoma (IMPC) of the breast has a high propensity for lymphovascular invasion and axillary lymph node metastasis and displays an ‘inside-out’ growth pattern, but the molecular mechanism of invasion, metastasis and cell polarity reversal in IMPC is unclear.

Methods

and Patients: Cell growth curves, tumor sphere formation assays, transwell assays, mouse xenograft model and immunofluorescence were evaluated to investigate the effects of miR-30c and MTDH. Dual luciferase reporter assays was performed to confirm that the MTDH (metadherin) 3′UTR bound to miR-30c. MiRNA in situ hybridization (ISH) and immunohistochemistry (IHC) were carried out on IMPC patient tissues for miR-30c and MTDH expression, respectively.

Results

We found miR-30c as a tumor suppressor gene in cell proliferation, metastasis and polarity reversal of IMPC. Overexpression of miR-30c inhibited cell growth and metastasis in vitro and in vivo. MiR-30c could directly target the MTDH 3′UTR. MiR-30c overexpression inhibited breast cancer cell proliferation, invasion and metastasis by targeting MTDH. Moreover, miR-30c/MTDH axis could also regulate cell polarity reversal of IMPC. By ISH and IHC analyses, miR-30c and MTDH were significantly correlated with tumor size, lymph nodule status and tumor grade, the ‘inside-out’ growth pattern, overall survival (OS) and disease-free survival (DFS) in IMPC patients.

Conclusions

Overall, miR-30c/MTDH axis was responsible for tumor proliferation, metastasis and polarity reversal. It may provide promising therapeutic targets and prognostic biomarkers for patients with IMPC.

Related collections

Most cited references 55

Record: found
Abstract: found
Article: not found

Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers.

G Calin, C Sevignani, C. D. Dumitru … (2004)

A large number of tiny noncoding RNAs have been cloned and named microRNAs (miRs). Recently, we have reported that miR-15a and miR-16a, located at 13q14, are frequently deleted and/or down-regulated in patients with B cell chronic lymphocytic leukemia, a disorder characterized by increased survival. To further investigate the possible involvement of miRs in human cancers on a genome-wide basis, we have mapped 186 miRs and compared their location to the location of previous reported nonrandom genetic alterations. Here, we show that miR genes are frequently located at fragile sites, as well as in minimal regions of loss of heterozygosity, minimal regions of amplification (minimal amplicons), or common breakpoint regions. Overall, 98 of 186 (52.5%) of miR genes are in cancer-associated genomic regions or in fragile sites. Moreover, by Northern blotting, we have shown that several miRs located in deleted regions have low levels of expression in cancer samples. These data provide a catalog of miR genes that may have roles in cancer and argue that the full complement of miRs in a genome may be extensively involved in cancers.

0 comments Cited 294 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Tumour invasion and metastasis initiated by microRNA-10b in breast cancer.

Li Ma, Julie Teruya-Feldstein, Robert A. Weinberg (2007)

MicroRNAs have been implicated in regulating diverse cellular pathways. Although there is emerging evidence that some microRNAs can function as oncogenes or tumour suppressors, the role of microRNAs in mediating cancer metastasis remains unexplored. Here we show, using a combination of mouse and human cells, that microRNA-10b (miR-10b) is highly expressed in metastatic breast cancer cells and positively regulates cell migration and invasion. Overexpression of miR-10b in otherwise non-metastatic breast tumours initiates robust invasion and metastasis. Expression of miR-10b is induced by the transcription factor Twist, which binds directly to the putative promoter of mir-10b (MIRN10B). The miR-10b induced by Twist proceeds to inhibit translation of the messenger RNA encoding homeobox D10, resulting in increased expression of a well-characterized pro-metastatic gene, RHOC. Significantly, the level of miR-10b expression in primary breast carcinomas correlates with clinical progression. These findings suggest the workings of an undescribed regulatory pathway, in which a pleiotropic transcription factor induces expression of a specific microRNA, which suppresses its direct target and in turn activates another pro-metastatic gene, leading to tumour cell invasion and metastasis.

0 comments Cited 192 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Hepatoma cell-secreted exosomal microRNA-103 increases vascular permeability and promotes metastasis by targeting junction proteins

Jian-Hong Fang, Zi-Jun Zhang, Li-Ru Shang … (2018)

Increased vascular permeability facilitates metastasis. Emerging evidence indicates that secreted microRNAs (miRNAs) may mediate the crosstalk between cancer and stromal cells. To date, whether and how secreted miRNAs affect vascular permeability remains unclear. Based on deep sequencing and quantitative PCR, we found that higher level of serum miR-103 was associated with higher metastasis potential of hepatocellular carcinoma (HCC). The in vitro endothelial permeability and transendothelial invasion assays revealed that the conditioned media or exosomes derived from high miR-103-expressing hepatoma cells increased the permeability of endothelial monolayers, but this effect was attenuated if exosome secretion of hepatoma cells was blocked by silencing ALIX and HRS or if miR-103 within hepatoma or endothelial cells was antagonized. Most importantly, pretreating endothelial monolayers with exosomes that were from stable miR-103-expressing hepatoma cells facilitated the transendothelial invasion of tumor cells, and this role of exosomes was abrogated by inhibiting miR-103 in endothelial cells. Further in vivo analyses disclosed that mice with xenografts of stable miR-103-expressing hepatoma cells exhibited higher vascular permeability in tumor, higher level of exosomal miR-103 and greater number of tumor cells in blood circulation, and increased rates of hepatic and pulmonary metastases, compared to control mice. Mechanism investigations revealed that hepatoma cell-secreted miR-103 could be delivered into endothelial cells via exosomes, and then attenuated the endothelial junction integrity by directly inhibiting the expression of VE-Cadherin (VE-Cad), p120-catenin (p120) and zonula occludens 1. Moreover, miR-103 could also promote tumor cell migration by repressing p120 expression in hepatoma cells.

0 comments Cited 186 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Shuai Li

Li Fu

Journal

Journal ID (nlm-ta): Heliyon

Journal ID (iso-abbrev): Heliyon

Title: Heliyon

Publisher: Elsevier

ISSN (Electronic): 2405-8440

Publication date PMC-release: 02 July 2024

Publication date Collection: 15 July 2024

Publication date (Electronic): 02 July 2024

Volume: 10

Issue: 13

Electronic Location Identifier: e33938

Affiliations

[a ]Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China

[b ]National Clinical Research Center of Cancer, Tianjin 300060, China

[c ]Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China

[d ]Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, China

[e ]Ministry of Education, Breast Cancer Innovation Team of the Ministry of Education, Tianjin 300060, China

[f ]Key Laboratory of Cancer Prevention and Therapy, State Key Laboratory of Breast Cancer Research, Tianjin 300060, China

[g ]Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China

[h ]Southern University of Science and Technology, School of Medicine, 1088 Xueyuan Road, Shenzhen, Guangdong 518055, China

[i ]Emory Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, 1365C Clifton Road, Atlanta, 30322, Georgia, USA

[j ]School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China

[k ]Gene Editing Center, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China

[l ]Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China

Author notes

[* ]Corresponding author. Department of Breast Pathology and Lab, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Ministry of Education, West Huanhu Road, Ti Yuan Bei, Hexi District, Tianjin 300060, China. fuli@ 123456tijmu.edu.cn

[** ]Corresponding author. Department of Breast Pathology and Lab, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Ministry of Education, West Huanhu Road, Ti Yuan Bei, Hexi District, Tianjin 300060, China. shuaili@ 123456tmu.edu.cn

[1]

These authors contributed equally to this work.

Article

Publisher Item ID: S2405-8440(24)09969-9 Publisher ID: e33938

DOI: 10.1016/j.heliyon.2024.e33938

PMC ID: 11279262

SO-VID: 50ef326e-7809-481c-947f-0f3cb6f66fb9

License:

This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).

History

Date received : 21 January 2024

Date revision received : 30 June 2024

Date accepted : 1 July 2024

Comments

Comment on this article

scite_

Smart Citations

Citing PublicationsSupportingMentioningContrasting

View Citations

See how this article has been cited at scite.ai

scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.

Most referenced authors 878

See all reference authors

MiR-30c suppresses the proliferation, metastasis and polarity reversal of tumor cell clusters by targeting MTDH in invasive micropapillary carcinoma of the breast

Read this article at

Abstract

Purpose

Methods

Results

Conclusions

Related collections

Karger: Oncology

Most cited references 55

Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers.

Tumour invasion and metastasis initiated by microRNA-10b in breast cancer.

Hepatoma cell-secreted exosomal microRNA-103 increases vascular permeability and promotes metastasis by targeting junction proteins

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 273

Most referenced authors 878