HMGA2 and Bach‐1 cooperate to promote breast cancer cell malignancy

Mansoori, Behzad; Mohammadi, Ali; Asadzadeh, Zahra; Shirjang, Solmaz; Minouei, Mahsa; Gaballu, Fereydoon Abedi; Shajari, Neda; Kazemi, Tohid; Gjerstorff, Morten F.; Duijf, Pascal H.G.; Baradaran, Behzad

doi:10.1002/jcp.28397

Cited by 36 publications

(33 citation statements)

References 49 publications

(77 reference statements)

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“…For example, researchers have found that knockdown of HMGA2 in mice could induce the pygmy phenotype with characteristic hypoplasia of mesenchymal tissue while overexpression of HMGA2 could increase the body size of mice and the incidence of certain tumors (Arlotta et al, ). Besides, HMGA2 could rarely be detected in adult tissues but is relatively highly expressed in a variety of benign and malignant tumors, such as breast cancer (Mansoori et al, ), colon cancer (Li et al, ), and lung cancer (Gao et al, ).…”

Section: Discussionmentioning

confidence: 99%

The protective effects of HMGA2 in the senescence process of bone marrow‐derived mesenchymal stromal cells

Yang

Wang

et al. 2020

J Tissue Eng Regen Med

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Bone marrow-derived mesenchymal stromal cells (MSCs) have been wildly applied to cell-based strategies for tissue engineering and regenerative medicine; however, they have to undergo the senescence process and thus appeared to be less therapeutic effective. HMGA2, a protein belonged to high mobility group A (HMGA) family, exhibits an inverse expression level related to embryonic development and acts as a developmental regulator in stem cell self-renewal progression. Therefore, we performed senescence-associated β-galactosidase (SA-β-gal) staining, transwell assay, to examine the changes of MSCs in different stages and then over-expressed HMGA2 in MSCs by lentivirus transfection. We found the percentage of SA-β-gal staining positive cells in MSCs from 24-month-old Sprague-Dawley (SD) rats (O-MSCs) was significantly higher compared with MSCs from 2-week-old SD rats (Y-MSCs), and the expression levels of P21 and P53, two senescence-related molecules, were also significantly up-regulated in O-MSCs than in Y-MSCs. In contrast, the HMGA2 expression level in O-MSCs was dramatically down-regulated in contrast to Y-MSCs. In additional, the migration ability in O-MSCs was significantly attenuated than in Y-MSCs. After successfully over-expressed HMGA2 in O-MSCs, the percentage of SAβ-gal staining positive cells and the expression levels of P21 and P53 were reduced, and the migration ability was improved compared with O-MSCs without treatment. Further, mRNA sequencing analysis revealed that overexpression of HMGA2 changed the expression of genes related to cell proliferation and senescence, such as Lyz2, Pf4, Rgs2, and Mstn. Knockdown of Rgs2 in HMGA2 overexpression O-MSCs could antagonize the protective effect of HMGA2 in the senescence process of O-MSCs.

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Section: Discussionmentioning

confidence: 99%

The protective effects of HMGA2 in the senescence process of bone marrow‐derived mesenchymal stromal cells

Yang

Wang

et al. 2020

J Tissue Eng Regen Med

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“…MicroRNAs (miRNAs) also belong to non-coding RNAs with the length of [18][19][20][21][22][23][24] nucleotides. MiRNAs can bind to 3'-untranslated region (3'-UTR) of target mRNAs and suppress the expression of mRNA, resulting in the loss of many biological functions.…”

Section: Introductionmentioning

confidence: 99%

“…[14,15] HMGA2 was reported to participate in cell progression of plenty of cancers including gastric cancer, breast cancer, lung cancer and CRC. [16][17][18][19] Despite a lot of researches on explaining the role of HMGA2 in CRC, how HMGA2 participate in the regulation of CRC needs to be further studied.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA 100146 Promotes Colorectal Cancer Progression by the MicroRNA 149/HMGA2 Axis

Liu

Mou

Shi

et al. 2021

Molecular and Cellular Biology

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Aim: Colorectal cancer (CRC) has developed into the third leading reason of cancer-associated death worldwide. Studies has confirmed that circular RNAs (circRNAs) sponge microRNAs (miRNAs) to regulate the function of downstream genes. This study aimed to expound the underlying mechanism of circRNA 100146 in CRC. Methods: The expression of circRNA 100146, miR-149 and high mobility group A2 (HMGA2) was detected by quantitative real time PCR (RT-qPCR). A series of bio-functional effects (cell viability, apoptosis, migration/invasion) were evaluated by methyl thiazolyl tetrazolium (MTT), flow cytometry, transwell. Protein level was measured by Western blot assay. The xenograft model was established for in vivo experiments. The interactions among circRNA 100146, miR-149 and HMGA2 were evaluated by dual-luciferase reporter assay, RNA immunoprecipitation assays, or RNA pulldown assay. Results: CircRNA 100146 was upregulated in CRC tissues and cells. CircRNA 100146 knockdown inhibited cell proliferation, promoted apoptosis and suppressed migration and invasion in vitro, and impeded tumor growth in vivo. Also, miR-149 was negalitively regulated by circRNA 100146, and targeted to HMGA2 and mediated its expression. Moreover, miR-149 interference abrogated the activities of silenced circRNA 100146 in proliferation, apoptosis, migration and invasion. Furthermore, HMGA2 overexpression abated the effects above caused by circRNA 100146 silencing, while the mutant on miR-149 binding sites in HMGA2 3’UTR lead to it losing this ability. Conclusion: CircRNA 100146 knockdown repressed proliferation, enhanced apoptosis and hindered migration and invasion in SW620 and SW480 cells through targeting miR-149/HMGA2 axis.

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“…HMGA2 is reported to be an oncogene that has been extensively studied in diverse tumors, such as colon, breast, and gastric cancer (Li et al, ;Mansoori et al, ;Sun, Qiao, Song, & Wang, ;Xi et al, ). HMGA2 can bind to the promoter of the cyclin gene, upregulates cyclin expression, accelerates the G2/M phase of the cell cycle, and enhances tumorigenesis (Fusco & Fedele, ).…”

Section: Discussionmentioning

confidence: 99%

Circ_0000267 promotes gastric cancer progression via sponging MiR‐503‐5p and regulating HMGA2 expression

Cai

Nie

Chen

et al. 2019

Molec Gen & Gen Med

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Background: Circular RNAs (circRNAs) are a class of newly discovered RNAs that attach great importance to modulate gene expression and biological function.Nonetheless, in gastric cancer (GC), the expression and function of circRNA are much less explored. In this study, circ_0000267 expression in GC was investigated and the function and mechanism of circ_0000267 was probed. Materials and Methods: Quantitative real-time PCR (qRT-PCR) was employed to detect circ_0000267, miR-503-5p, and HMGA2 expression. Immunohistochemistry and western blot were adopted to detect HMGA2 and epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin and N-cadherin) expression in GC tissues and cells, respectively. GC cell lines with circ_0000267 overexpressed and knocked down were constructed, and CCK-8 assay, BrdU assay, scratch healing assay, and transwell assay were employed to assess the effect of circ_0000267 on the proliferation and metastasis of GC cells. Besides, dual-luciferase reporter gene assay was adopted to verify the targeting relationship between circ_0000267 and miR-503-5p. Results: Circ_0000267 showed a significant upregulation in GC tissues and cell lines, and its high expression level was extremely linked to the increased tumor diameter and local lymph node metastasis. Circ_0000267 overexpression accelerated GC cell proliferation, metastasis, and EMT processes, while knocking down circ_0000267 led to the opposite effect. From the perspective of mechanism, circ_0000267 promoted the progression of GC through adsorbing miR-503-5p and upregulating HMGA2 expression. Conclusion: Circ_0000267 is an oncogenic circRNA that affects the progression of GC, which participates in promotion of GC proliferation, migration, invasion, and EMT via modulating the miR-503-5p/HMGA2 axis. K E Y W O R D Scirc_0000267, Gastric cancer, HMGA2, miR-503-5p 2 of 12 | XIAOPENG Et Al. F I G U R E 2 circ_0000267 promoted GC cell proliferation, movement, migration, and invasion. (a) circ_0000267 plasmid was transfected into MGC-803 cells, and circ_0000267 in SGC-7901 cells was knocked down with siRNA, and the transfection efficiency was examined by qRT-PCR. (b-d) The proliferation of GC cells was examined using the CCK-8 assay and the BrdU assay. (e, f) Scratch healing experiments were used to detect the movement of GC cells. (g) Transwell assay was used to detect GC cell migration and invasion. (h) Western blot was used to detect the expression of EMT-related marker molecules, including E-cadherin and N-cadherin.

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HMGA2 and Bach‐1 cooperate to promote breast cancer cell malignancy

Cited by 36 publications

References 49 publications

The protective effects of HMGA2 in the senescence process of bone marrow‐derived mesenchymal stromal cells

The protective effects of HMGA2 in the senescence process of bone marrow‐derived mesenchymal stromal cells

Circular RNA 100146 Promotes Colorectal Cancer Progression by the MicroRNA 149/HMGA2 Axis

Circ_0000267 promotes gastric cancer progression via sponging MiR‐503‐5p and regulating HMGA2 expression

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