MiR-4638-3p regulates transforming growth factor-β1-induced activating transcription factor-3 and cell proliferation, invasion, and apoptosis in human breast cancer cells

Akshaya, R.L.; Rohini, M.; He, Zhiming; Partridge, Nicola C.; Selvamurugan, N.

doi:10.1016/j.ijbiomac.2022.09.286

Cited by 11 publications

(10 citation statements)

References 43 publications

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“…We previously reported that miR-4638-3p directly targeted ATF3. 18 In this study, silencing of circ_DISP3 decreases ATF3 expression in hBC cells (Fig. 4).…”

Section: Circ_disp3 Directly Interacted With Mir-4638-3p In Hbc Cellssupporting

confidence: 57%

“…Akshaya et al reported that TGF-β1 treatment substantially reduced the expression of miR-4638-3p in BC cells and that overexpression suppressed BC progression and invasion and induced apoptosis by targeting ATF3. 18 This study emphasizes the role of miR-4638-3p as a therapeutic target for bone-metastatic BC.…”

Section: -3p Was Responsible For the Increased Expression Of Atf3mentioning

confidence: 83%

“…We previously reported that TGF-β1 promoted BC progression and metastasis via down-regulating the expression of miR-4638-3p, which directly targets ATF3 in hBC cells. 18 Therefore, in this study, we identified the molecular mechanism by which TGF-β1 regulated the circRNA/miR-4638-3p/ATF3 axis in hBC cells. We found that TGF-β1 substantially increased the expression of circ_ DISP3, which functioned as a ceRNA and directly targeted miR-4638-3p.…”

Section: Introductionmentioning

confidence: 97%

“…Since ATF3 has few druggable sites like other transcription factors, direct targeting ATF3 for translational research is difficult. 18 Increasing evidence suggests the involvement of noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and circular RNAs (circRNAs), in regulating BC pathogenesis. [19][20][21] MiRNAs are small endogenous ncRNAs of 20-25 nucleotides in length.…”

Section: Introductionmentioning

confidence: 99%

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Transforming Growth Factor-β1-mediated Regulation of circ_DISP3 and ATF3 in Human Triple-negative Breast Cancer Cells

Mohan,

Bharathy,

Induja

et al. 2023

Gene Expr

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Background and objectives: Transforming growth factor-beta 1 (TGF-β1) stimulates activating transcription factor 3 (ATF3), and it is required for the expression of cell proliferation, invasion, and bone metastasis genes in human breast cancer cells. Noncoding RNAs have a crucial role in both physiological and pathological circumstances in the expression of genes. We previously determined the direct targeting of ATF3 by miR-4638-3p, downregulated by TGF-β1 in human triple-negative breast cancer cells (MDA-MB231). This study identified the molecular mechanism of downregulating ATF3 targeting miR-4638-3p via circRNA in MDA-MB231 cells. Methods:In-silico analyses were used to identify the list of circRNAs targeting miR-4638-3p. RT-qPCR was performed to determine the expression of shortlisted circRNAs in MDA-MB231 cells. Transient transfection and western blot analyses were carried out to identify the functional role of circ_DISP3 in MDA-MB231 cells. A dual-luciferase reporter assay was used to identify the direct binding of circ_DISP3 and miR-4638-3p. Results:There was an inverse correlation between the expression of circ_DISP3 and miR-4638-3p in these cells. Antisense oligosmediated silencing of circ_DISP3 restored the function of miR-4638-3p, resulting in the downregulation of ATF3 in MDA-MB231 cells. Furthermore, a luciferase reporter assay identified the direct binding of circ_DISP3 toward miR-4638-3p in these cells.Conclusions: TGF-β1 influenced circ_DISP3 to sponge miR-4638-3p, promoting ATF3 expression in MDA-MB231 cells. Silencing this circRNA caused the restoration of miR-4638-3p activity toward targeting ATF3 in these cells. Hence, we suggest that the

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“…We previously reported that miR-4638-3p directly targeted ATF3. 18 In this study, silencing of circ_DISP3 decreases ATF3 expression in hBC cells (Fig. 4).…”

Section: Circ_disp3 Directly Interacted With Mir-4638-3p In Hbc Cellssupporting

confidence: 57%

Section: -3p Was Responsible For the Increased Expression Of Atf3mentioning

confidence: 83%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Transforming Growth Factor-β1-mediated Regulation of circ_DISP3 and ATF3 in Human Triple-negative Breast Cancer Cells

Mohan,

Bharathy,

Induja

et al. 2023

Gene Expr

View full text Add to dashboard Cite

show abstract

“…Because of their ability to target mRNAs and their effective use as molecular markers, miRNAs have accrued increasing interest [ 30 , 31 ]. For instance, miR-4638-3p targets ATF3 in breast cancer cells, effectively suppressing cancer progression and bone metastasis [ 32 ]. MiRNAs are transcribed in the nucleus by RNA polymerase II (RNA Pol II), resulting in sequences characterized by a stem-loop structure called a primary miRNA (pri-miRNA).…”

Section: Introductionmentioning

confidence: 99%

A potential function for MicroRNA-124 in normal and pathological bone conditions

Kolipaka,

Magesh,

Bharathy

et al. 2024

Non-coding RNA Research

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In vivo validation of the functional role of MicroRNA-4638-3p in breast cancer bone metastasis

Akshaya,

Saranya,

Salomi

et al. 2024

J Cancer Res Clin Oncol

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Purpose Skeletal metastases are increasingly reported in metastatic triple-negative breast cancer (BC) patients. We previously reported that TGF-β1 sustains activating transcription factor 3(ATF3) expression and is required for cell proliferation, invasion, and bone metastasis genes. Increasing studies suggest the critical regulatory function of microRNAs (miRNAs) in governing BC pathogenesis. TGF-β1 downregulated the expression of miR-4638-3p, which targets ATF3 in human BC cells (MDA-MB-231). In the present study, we aimed to identify the functional role of miR-4638-3p in BC bone metastasis by the caudal artery injection of the MDA-MB-231 cells overexpressing mir-4638 in the mice. Methods MDA-MB-231 cells overexpressing miR-4638 were prepared by stable transfections. Reverse transcriptase quantitative PCR was carried out to determine the expression of endogenous miR-4638-3p and bone resorption marker genes. X-ray, micro-CT, and Hematoxylin & Eosin studies were used to determine osteolytic lesions, trabecular structure, bone mineral density, and micrometastasis of cells. Results The mice injected with MDA-MB-231 cells overexpressing miR-4638-3p decreased the expression of bone resorption marker genes, compared to MDA-MB-231 cells injection. Reduced osteolytic lesions and restored bone density by MDA-MB-231 cells overexpressing miR-4638-3p were observed. Similarly, the mice injected with MDA-MB-231 cells overexpressing miR-4638-3p showed a better microarchitecture of the trabecular network. A few abnormal cells seen in the femur of MDA-MB-231 cells-injected mice were not found in MDA-MB-231 cells overexpressing miR-4638. Conclusion The identified functional role of ATF3 targeting miR-4638-3p in BC bone metastasis in vivo suggests its candidature as BC therapeutics in the future.

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MiR-4638-3p regulates transforming growth factor-β1-induced activating transcription factor-3 and cell proliferation, invasion, and apoptosis in human breast cancer cells

Cited by 11 publications

References 43 publications

Transforming Growth Factor-β1-mediated Regulation of circ_DISP3 and ATF3 in Human Triple-negative Breast Cancer Cells

Transforming Growth Factor-β1-mediated Regulation of circ_DISP3 and ATF3 in Human Triple-negative Breast Cancer Cells

A potential function for MicroRNA-124 in normal and pathological bone conditions

In vivo validation of the functional role of MicroRNA-4638-3p in breast cancer bone metastasis

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