Lnc RNA H19 is associated with poor prognosis in breast cancer patients and promotes cancer stemness

Shima, Hidetaka; Kida, Kumiko; Adachi, Shoko; Yamada, Akihiro; Sugae, Sadatoshi; Narui, Kazutaka; Miyagi, Yohei; Nishi, Mayuko; Ryo, Akihide; Murata, Soichiro; Taniguchi, Hideki; Ichikawa, Yasushi; Ishikawa, Takashi; Endo, Itaru

doi:10.1007/s10549-018-4793-z

Cited by 81 publications

(70 citation statements)

References 38 publications

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“…However, studies have confirmed that H19 is associated with the stem cell phenotype of aldehyde dehydrogenase 1 (ALDH1)‐positive breast cancer. H19 can affect breast cancer stem cells and lead to poor prognosis in patients with breast cancer . Therefore, we knocked out H19 from resistant CC cells; this action may lead to changes in the characteristics of CC stem cells and in turn result in increased apoptosis under the action of chemotherapeutic drugs and diminished ability to proliferate, migrate, and invade.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA H19 promotes chemotherapy resistance in choriocarcinoma cells

Tan

et al. 2019

J of Cellular Biochemistry

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Choriocarcinoma (CC) is a trophoblast tumor prone to early distant organ metastases. At present, the main treatment for CC is chemotherapy, but chemotherapy resistance readily occurs and leads to treatment failure. H19 is a long noncoding RNA, and its abnormal expression has been found in various tumors, including CC. H19 is also considered to be related to the drug resistance mechanism of the same cancers. To investigate the role of H19 in drug‐resistant CC cells, the following experiments were designed. We used human CC cell line JEG‐3 to establish cell lines resistant to methotrexate and 5‐fluorouracil (JEG‐3/MTX and JEG‐3/5‐FU) and detected the expression of H19 in JEG‐3, JEG‐3/MTX, JEG‐3/5‐FU cells, JEG‐3 with MTX, and JEG‐3 with 5‐FU. We found that the expression of H19 in the JEG‐3/MTX and JEG‐3/5‐FU cells were significantly higher than that in JEG‐3 cells. JEG‐3 cells were treated with MTX or 5‐FU for and quantitative real‐time polymerase chain reaction assay revealed that H19 messenger RNA expression increased. Furthermore, after H19 was knocked out, the drug resistance index of the JEG‐3/MTX and JEG‐3/5‐FU cells decreased; the proliferation, migration, and invasion ability diminished significantly; and apoptosis increased significantly. Finally, we detected the total and phosphorylation protein expression of phosphatidylinositol‐3‐kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) in the JEG‐3/MTX and JEG‐3/5‐FU cells. The total protein of PI3K, AKT, and mTOR in the H19 knockout resistant cells showed no significant change relative to those in the H19 non‐knockout resistant cells, whereas the phosphorylated proteins of PI3K, AKT, and mTOR were significantly decreased. Phosphorylated proteins of PI3K, AKT, and mTOR in the JEG‐3/MTX and JEG‐3/5‐FU cells were significantly higher than that in JEG‐3 cells. After using inhibition of phosphorylated PI3K/AKT/mTOR, the proliferation, migration, and invasion ability of the JEG‐3/MTX and JEG‐3/5‐FU cells diminished significantly; and apoptosis increased significantly. On the basis of the above experiments, we concluded that H19 is related to the drug resistance of CC, and the knockout of H19 can reduce the drug resistance of resistant CC cells; and decrease the proliferative, migratory, and invasive ability; and increase the apoptosis. PI3K/AKT/mTOR pathway might be involved in H19‐mediated effects. H19 is expected to be a therapeutic target for the treatment of drug‐resistant chorionic carcinoma.

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Section: Discussionmentioning

confidence: 99%

Long noncoding RNA H19 promotes chemotherapy resistance in choriocarcinoma cells

Tan

et al. 2019

J of Cellular Biochemistry

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“…Another developmentally important lncRNA, H19, promotes cancer progression in several cancers including breast [52,[86][87][88] and is enriched in the ALDH high breast CSC populations of TNBCs [63]. H19 sponges miRNA tumor suppressor, let-7, facilitating a concomitant increase in the breast CSC-enriched pluripotency factor LIN28.…”

Section: H19mentioning

confidence: 99%

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

Brown

Wasson

Marcato

2020

Cells

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Treatment decisions for breast cancer are based on staging and hormone receptor expression and include chemotherapies and endocrine therapy. While effective in many cases, some breast cancers are resistant to therapy, metastasize and recur, leading to eventual death. Higher percentages of tumor-initiating cancer stem cells (CSCs) may contribute to the increased aggressiveness, chemoresistance, and worse outcomes among breast cancer. This may be particularly true in triple-negative breast cancers (TNBCs) which have higher percentages of CSCs and are associated with worse outcomes. In recent years, increasing numbers of long non-coding RNAs (lncRNAs) have been identified as playing an important role in breast cancer progression and some of these have been specifically associated within the CSC populations of breast cancers. LncRNAs are non-protein-coding transcripts greater than 200 nucleotides which can have critical functions in gene expression regulation. The preclinical evidence regarding lncRNA antagonists for the treatment of cancer is promising and therefore, presents a potential novel approach for treating breast cancer and targeting therapy-resistant CSCs within these tumors. Herein, we summarize the lncRNAs that have been identified as functionally relevant in breast CSCs. Furthermore, our review of the literature and analysis of patient datasets has revealed that many of these breast CSC-associated lncRNAs are also enriched in TNBC. Together, this suggests that these lncRNAs may be playing a particularly important role in TNBC. Thus, certain breast cancer-promoting/CSC-associated lncRNAs could be targeted in the treatment of TNBCs and the CSCs within these tumors should be susceptible to anti-lncRNA therapy.

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“…The long non-coding RNA (lncRNA) H19 can function either as a tumor promoter or as a tumor suppressor, depending on the type of cancer, development stage, or molecular background [8][9][10][11]. The H19 was upregulated in many tumors including esophageal squamous cell carcinoma [12], lung cancer [13], gastric cancer [14], and breast cancer [15], and H19 overexpression contributes to poor prognosis in these patients. However, in osteosarcoma [16] and renal cell carcinoma [17], H19 overexpression contributes to a good prognosis.…”

Section: Introductionmentioning

confidence: 99%

Targeted inhibition of long non-coding RNA H19 blocks anaplastic thyroid carcinoma growth and metastasis

Zhang

et al. 2019

Bioengineered

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Long non-coding RNA H19 (H19) is highly expressed in cancers and is considered to highly correlate with the extent of malignant degree. The present study was performed to determine the expression levels of H19 in anaplastic thyroid carcinoma (ATC) tissues and the role of H19 in ATC 8505C cells in vitro and in vivo. Expression of H19 was detected in 19 ATC and 19 normal thyroid tissues by real-time quantitative polymerase chain reaction. Utilizing the siRNA or short hairpin RNA (shRNA) directed against human H19 (H19 siRNA or shRNA H19) depleted H19 in ATC 8505C cells and characterized the outcomes. The results showed that H19 was overexpressed in ATC tissues. Targeting H19 inhibited proliferation, migration, and invasion and induced apoptosis in 8505C cells in vitro and inhibited tumorigenesis and metastasis in vivo. Therefore, the H19 might be an effective target for ATC molecular therapy.

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Lnc RNA H19 is associated with poor prognosis in breast cancer patients and promotes cancer stemness

Abstract: This study indicated that H19 was associated with stem cell phenotype in ALDH1-positive breast cancer. H19 regulates CSC and is associated with poor prognosis in breast cancer patients, particularly in triple-negative subtype.

Cited by 81 publications

References 38 publications

Long noncoding RNA H19 promotes chemotherapy resistance in choriocarcinoma cells

Long noncoding RNA H19 promotes chemotherapy resistance in choriocarcinoma cells

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

Targeted inhibition of long non-coding RNA H19 blocks anaplastic thyroid carcinoma growth and metastasis

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