microRNA‐30d mediated breast cancer invasion, migration, and EMT by targeting KLF11 and activating STAT3 pathway

Abstract

miR-30d has been shown to play pivotal roles in cancer development, and has the potential to act as a diagnostic biomarker and therapeutic target in breast cancer. However, the specific function and molecular mechanism of miR-30d in breast cancer cell growth and metastasis is still unknown. The present study seeks to shed light on the potential contribution of the MiR-30d-KLF-11-STAT3 pathway in breast cancer. The results revealed that miR-30d levels were markedly increased in the breast cancer cell lines BT474, MDA-MB-231, HCC197, and MDA-MB-468 compared with the non-tumor mammary gland MCF10A cell line. Furthermore, the miR-30d mimic increased BT474 and MDA-MB-231 breast cancer cell survival, inhibited apoptosis and increased Bcl-2 expression, whilst inhibited Bax protein levels. miR-30d mimics promote BT474 and MDA-MB-231 cell migration, invasion, and mediate the EMT phenotype. However, miR-30d inhibitors reverse all of the effects of miR-30d mimics on breast cancer cell biology. Also, we observed that KLF-11 is a direct target of miR-30d and KLF-11 and pSTAT3 expression are determined by miR-30d. Finally, the results suggest that miR-30d plays essential roles in breast cancer cells in a manner that is dependent on the levels of KLF-1 and pSTAT3. In summary, miR-30d appears to be a novel diagnostic biomarker and treatment target in breast cancer.

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

“…Moreover, STAT3 was upregulated in TGF‐β1‐induced EMT during renal fibrosis, implying that STAT3 is an innovative target for the prevention of fibrosis . Furthermore, there are many mediators that induce EMT through the activation of STAT3, such as Pin1, HOXB8, miR‐30d, and IL‐6 …”

“…111 Furthermore, there are many mediators that induce EMT through the activation of STAT3, such as Pin1, HOXB8, miR-30d, and IL-6. [112][113][114][115] Sepantronium bromide is an inhibitor of survivin that exhibits anticancer properties in multiple cancer types. A recent study revealed that sepantronium bromide reduced the invasion of glioblastoma induced by radiation and reversed EMT by targeting STAT3.…”

Genetic Variations in miR-30 Family Member Regulatory Regions Are Associated with Breast Cancer Risk in a Chinese Population

“…Still, other work has found that miR-30c can inhibit the induction of Serpine 1 by TGF-β-induced Serpine 1, driving fibrin degradation and disrupting angiogenesis within the tumor microenvironment in order to constrain tumor progression [14]. The migration and invasion of the BT474 and MDA-MB-231 cancer cell lines were shown to be impaired by miR-30d, which was able to target KLF11 and the STAT3 pathway in order to regulate tumor cell epithelial-mesenchymal transition [7]. IRS1 has also been shown to be targeted by miR-30e, leading to impaired breast cancer tumor growth and chemoresistance [15].…”

“…Recently, accumulating evidence indicates that miRNAs may act as either tumor suppressors or oncogenes in the genesis of diverse cancer types [3,4]. The dysregulated expression of certain miRNAs, including miR-30 family members, has been closely linked to the onset and progression of breast cancer [5][6][7]. The miR-30 family includes 6 mature miRNAs (miR-30a, miR-30b, miR-30c-1, miR-30c-2, miR-30d, and miR-30e) that are separately encoded on chromosomes 1, 6, and 8.…”

“…The miR-30 family includes 6 mature miRNAs (miR-30a, miR-30b, miR-30c-1, miR-30c-2, miR-30d, and miR-30e) that are separately encoded on chromosomes 1, 6, and 8. In most studies, these miR-30 family members have been shown to function as tumor suppressors that act to constrain the development of various cancers [7][8][9][10][11][12][13][14][15]. Among the miR-30 members, miR-30a had drawn much attention due to its functions in inhibiting primary tumor growth or metastasis formation in several cancer types, especially in breast cancer [8][9][10][11][12].…”