The Missing Lnc: The Potential of Targeting Triple-Negative Breast Cancer and Cancer Stem Cells by Inhibiting Long Non-Coding RNAs

Brown, Justin M.; Wasson, Marie-Claire D.; Marcato, Paola

doi:10.3390/cells9030763

Cited by 26 publications

(28 citation statements)

References 136 publications

(179 reference statements)

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“…LncRNAs have been shown to regulate tumorigenesis, metastasis and involved in the therapy in several types of cancer, 37 such as gastric cancer, 38 lung cancer 39 and breast cancer. 40,41 Currently, a number of abnormally expressed LncRNAs have been identified in cervical cancer and participated in progress of cervical cancer. 42,43 DLEU2 encodes a long noncoding RNA that is polyadenylated and spliced.…”

mentioning

confidence: 99%

<p>Knockdown of LncRNA DLEU2 Inhibits Cervical Cancer Progression via Targeting miR-128-3p</p>

Wang

Hang

et al. 2020

OTT

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Objective: Cervical cancer is one of the most common female malignancies worldwide and represents a major global health challenge. The fast growth of tumor and high rates of metastasis still lead to a poor prognosis of cervical cancer patients. It is urgent to clarify the mechanism and identify predictive biomarkers for the treatment of cervical cancer. Long non-coding RNAs (LncRNAs) have been identified in cervical cancer and are related to malignant phenotypes of cervical cancer cells. However, the roles and mechanism of LncRNA deleted in lymphocytic leukemia (DLEU2) in the tumorigenesis and progression of cervical cancer remain unknown. Materials and Methods: qPCR was performed to analyze the expression of DLEU2, Cyclin D1, CDK4, Bax, Bcl2 and mi-128-3p. Western blot was performed to detect the cell cycle hallmarks expression. CCK8 was used to examine cell proliferation. Cellular apoptosis was analyzed by Hoechst 33,258 staining and AV/PI staining with flow cytometry. Cell cycle was analyzed by flow cytometry. The xenograft model in nude mice was used to elucidate the function of DLEU2 in vivo. Bioinformatics analysis and luciferase reporter assay were proceeded to clarify whether miR-128-3p directly binds with lncRNA DLEU2. Pull-down assay and RNA-binding protein immunoprecipitation assay were used for exploring the relationship between DLEU2 and miR-128-3p. Results: We demonstrated that DLEU2 was upregulated in cervical cancer tumor tissues. Downregulation of DLEU2 inhibited cell proliferation, induced apoptosis and cell cycle arrest at G2/M phase of cervical cancer cells in vitro, and suppressed tumor growth in vivo. Further, LncRNA DLEU2 is one of the targets of miR-128-3p. miR-128-3p inhibitor abrogated the cell proliferation suppressed by knockdown of DLEU2, apoptosis induced by knockdown of DLEU2 and reversed the expression of cell cycle hallmarks regulated by knockdown of DLEU2. Conclusion: Taken together, these results suggested knockdown of DLEU2 inhibited cervical cancer progression via targeting miR-128-3p.

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confidence: 99%

<p>Knockdown of LncRNA DLEU2 Inhibits Cervical Cancer Progression via Targeting miR-128-3p</p>

Wang

Hang

et al. 2020

OTT

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“…Indeed, lncRNAs represent a family of >200 nucleotide-long transcribed RNAs with described roles in primarily regulating gene expression in normal physiology and in disease settings, including cancer 18,19 . Whereas activities of individual lncRNAs of relevance to TNBC biology are being identified at a fast pace 20 , functions for the overwhelming members of the family are still outstanding. We found that MSCs induced robust LINC01119 expression in neighboring TNBC cells, which was sufficient, on its own, in promoting cancer cell growth in multiple contexts in vitro, as well as tumorigenesis in immunecompromised mice.…”

Section: Introductionmentioning

confidence: 99%

The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer

Schmoellerl

Mariani

et al. 2021

npj Breast Cancer

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The development of triple-negative breast cancer (TNBC) is critically regulated by certain tumor-microenvironment-associated cells called mesenchymal stem/stromal cells (MSCs), which we and others have shown promote TNBC progression by activating pro-malignant signaling in neighboring cancer cells. Characterization of these cascades would better our understanding of TNBC biology and bring about therapeutics that eliminate the morbidity and mortality associated with advanced disease. Here, we focused on the emerging class of RNAs called long non-coding RNAs or lncRNAs and utilized a MSC-supported TNBC progression model to identify specific family members of functional relevance to TNBC pathogenesis. Indeed, although some have been described to play functional roles in TNBC, activities of lncRNAs as mediators of tumor-microenvironment-driven TNBC development remain to be fully explored. We report that MSCs stimulate robust expression of LINC01119 in TNBC cells, which in turn induces suppressor of cytokine signaling 5 (SOCS5), leading to accelerated cancer cell growth and tumorigenesis. We show that LINC01119 and SOCS5 exhibit tight correlation across multiple breast cancer gene sets and that they are highly enriched in TNBC patient cohorts. Importantly, we present evidence that the LINC01119-SOCS5 axis represents a powerful prognostic indicator of adverse outcomes in TNBC patients, and demonstrate that its repression severely impairs cancer cell growth. Altogether, our findings identify LINC01119 as a major driver of TNBC development and delineate critical non-coding RNA theranostics of potential translational utility in the management of advanced TNBC, a class of tumors in most need of effective and targeted therapy.

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“…This differentiation and de-differentiation are closely related to EMT. Some authors have shown that the metastatic ability of CSC with EMT properties is enhanced, which led to the concept of metastatic stem cells ( 12 , 13 ). This is mainly due to the loss of tight junctions and cell adhesion after acquiring the EMT phenotype, which prepares the cells for migration to new organs.…”

Section: Introductionmentioning

confidence: 99%

LncRNA-42060 Regulates Tamoxifen Sensitivity and Tumor Development via Regulating the miR-204-5p/SOX4 Axis in Canine Mammary Gland Tumor Cells

et al. 2021

Front. Vet. Sci.

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Tamoxifen is the drug of choice for endocrine therapy of breast cancer. Its clinical use is limited by the development of drug resistance. There is increasing evidence that long non-coding RNAs (lncRNAs) are associated with tumor drug resistance. Therefore, we established two TAM-resistant cell lines, CHMpTAM and CHMmTAM. The different expression levels of lncRNA and miRNA in CHMmTAM and CHMm were screened by RNA sequencing, and the lncRNA-miRNA interactions were analyzed. LncRNA ENSCAFG42060 (lnc-42060) was found to be significantly upregulated in drug-resistant cells and tumor tissues. Further functional validation revealed that the knockdown of lnc-42060 inhibited proliferation, migration, clone formation, restoration of TAM sensitivity, and reduction of stem cell formation in drug-resistant cells, whereas overexpression of lnc-4206 showed opposite results. Bioinformatics and dual-luciferase reporter gene assays confirmed that lnc-42060 could act as a sponge for miR-204-5p, further regulating SOX4 expression activity and thus influencing tumor cell progression. In conclusion, we screened lncRNAs and miRNAs associated with TAM resistance in canine mammary gland tumor cells for the first time. lnc-42060 served as a novel marker that may be used as an important biomarker for future diagnosis and treatment.

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The Missing Lnc: The Potential of Targeting Triple-Negative Breast Cancer and Cancer Stem Cells by Inhibiting Long Non-Coding RNAs

Cited by 26 publications

References 136 publications

<p>Knockdown of LncRNA DLEU2 Inhibits Cervical Cancer Progression via Targeting miR-128-3p</p>

<p>Knockdown of LncRNA DLEU2 Inhibits Cervical Cancer Progression via Targeting miR-128-3p</p>

The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer

LncRNA-42060 Regulates Tamoxifen Sensitivity and Tumor Development via Regulating the miR-204-5p/SOX4 Axis in Canine Mammary Gland Tumor Cells

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