Dysregulation of miRNA in chronic hepatitis B is associated with hepatocellular carcinoma risk after nucleos(t)ide analogue treatment

Wakasugi, Hideki; Takahashi, Hideaki; Niinuma, Takeshi; Kitajima, Hiroshi; Oikawa, Ritsuko; Matsumoto, Naoki; Takeba, Yuko; Otsubo, Takehito; Takagi, Masayuki; Ariizumi, Yasushi; Suzuki, Michihiro; Okuse, Chiaki; Iwabuchi, Shogo; Nakano, Masayuki; Akutsu, Noriyuki; Kang, Jae-Heon; Matsui, Takeshi; Yamada, Noriko; Sasaki, Hajime; Yamamoto, Eiko; Kai, Masahiro; Sasaki, Yasushi; Sasaki, Shigeru; Tanaka, Yasuhito; Yotsuyanagi, Hiroshi; Tsutsumi, Takeshi; Yamamoto, Hiroyuki; Tokino, Takashi; Nakase, Hiroshi; Suzuki, Hiromu; Itoh, Fumio

doi:10.1016/j.canlet.2018.07.019

Cited by 19 publications

(16 citation statements)

References 56 publications

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“…Moreover, increasing expression thereof during the development of fibrosis of the liver and progressive liver fibrosis have been posited in the late stages of various chronic liver diseases. Research has demonstrated that miR-140-3p has a pro-fibrotic effect in the mammary glands14 and is deeply involved in liver disorders,121516 including hepatic impact injury, non-alcoholic fatty liver disease, and hepatocellular carcinoma. Thus, we planned to investigate the role of miR-140-3p in HSC activation and its molecular signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

miR-140-3p Knockdown Suppresses Cell Proliferation and Fibrogenesis in Hepatic Stellate Cells via PTEN-Mediated AKT/mTOR Signaling

Huang

et al. 2019

Yonsei Med J

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Purpose Liver fibrosis is a major cause of morbidity and mortality and the outcome of various chronic liver diseases. Activation of hepatic stellate cells (HSCs) is the key event in liver fibrosis. Studies have confirmed that miR-140-3p plays a potential regulatory effect on HSC activation. However, whether miR-140-3p mediates the liver fibrosis remains unknown. Materials and Methods Expression of miR-140-3p was detected by real-time quantitative PCR (qPCR). Cell proliferation was measured by MTT, while cell apoptosis rate was determined via flow cytometry. Western blot assay was used to detect the expression of cleaved PARP. The fibrogenic effect was evaluated by expression of α-smooth muscle actin and desmin. Functional experiments were performed in transforming growth factor β1 (TGF-β1)-induced HSC-T6 cells with transfection of anti-miR-140-3p and/or siPTEN. Target binding between miR-140-3p and PTEN was predicted by the TargetScan database and identified using luciferase reporter assay and RNA immunoprecipitation. Results TGF-β1 induced the activation of HSC-T6 cells, and miR-140-3p expression varied according to HSC-T6 cell activation status. Knockdown of miR-140-3p reduced cell proliferation and the expressions of α-SMA and desmin, as well as increased apoptosis, in TGF-β1-induced HSC-T6 cells, which could be blocked by PTEN silencing. Additionally, inactivation of the AKT/mTOR signaling pathway stimulated by miR-140-3p knockdown was abolished when silencing PTEN expression. PTEN was negatively regulated by miR-140-3p via direct binding in HSC-T6 cells. Conclusion miR-140-3p is an important mediator in HSC-T6 cell activation, and miR-140-3p knockdown suppresses cell proliferation and fibrogenesis in TGF-β1-induced HSC-T6 cells, indicating that miR-140-3p may be a potential novel molecular target for liver fibrosis.

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Section: Introductionmentioning

confidence: 99%

miR-140-3p Knockdown Suppresses Cell Proliferation and Fibrogenesis in Hepatic Stellate Cells via PTEN-Mediated AKT/mTOR Signaling

Huang

et al. 2019

Yonsei Med J

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“…miR-101-3p is a member of the miR-101 family, and a recent study indicated that it has tumor suppressor effects in patients with NSCLC ( 16 ). However, to the best of our knowledge, a limited number of studies have addressed the association between miR-101-3p and adjuvant chemotherapy in patients with NSCLC ( 17 – 19 ).…”

Section: Introductionmentioning

confidence: 99%

Prognostic implications of decreased microRNA‑101‑3p expression in patients with non‑small cell lung cancer

et al. 2018

Oncol Lett

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To investigate the expression level of microRNA-101-3p (miR-101-3p) and its possible association with progression, prognosis and chemotherapy in patients with non-small cell lung cancer (NSCLC), the Gene Expression Omnibus (GEO) database was used. Quantitative polymerase chain reaction was used to verify the expression in 327 NSCLC and 42 adjacent normal lung tissues, of which 42 viable tissues were paired with nearby normal lung tissues. Based on the Cox regression model, univariate and multivariate analyses were used to address the factors that had effects on overall survival (OS) and disease-free survival (DFS) rate. Data from the GEO database demonstrated that the miR-101-3p expression in NSCLC was downregulated, compared with normal lung cancer. Survival analysis through univariate and multivariate models indicated that the miR-101-3p expression level was a crucial risk factor for OS and DFS in patients with NSCLC. A number of clinical parameters were determined to be associated with miR-101-3p expression, including tumor diameter, lymph node metastasis and tumor-node-metastasis stage. Adjuvant chemotherapy with high expression of miR-101-3p was determined to increase OS and DFS in patients with NSCLC, compared with patients with de novo or low expression of miR-101-3p. The present results demonstrated that miR-101-3p expression levels were associated with NSCLC progression and prognosis, which indicated that miR-101-3p may serve as a biomarker for patients with NSCLC who have received adjuvant chemotherapy.

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“…Decreased expression levels of let-7g were reported in many types of cancer, including hepatocellular carcinoma (HCC) [15,18], lung cancer [29], breast cancer [16] and gastric cancer [30]. In HCC, a lower level of let-7g was reported to be correlated with metastasis and poor overall survival [15].…”

Section: Discussionmentioning

confidence: 99%

“…In let-7 mutant nematodes, seam cells fail to exit the cell cycle, leading to continuous seam cell division and the death of the worms, so the name lethal-7 was given to it after this discovery [11]. There are 13 kinds of let-7 in humans, among which let-7g has been proven to be tightly associated with hepatocellular carcinoma (HCC), non-small cell lung tumors, breast cancer and CRC [13,14,15,16,17,18]. Previous studies observed the reduction of let-7g in tumor tissues of metastatic HCC patients.…”

Section: Introductionmentioning

confidence: 99%

Functional Effects of let-7g Expression in Colon Cancer Metastasis

Chang

Wong

Huang

et al. 2019

Cancers

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MicroRNA regulation is crucial for gene expression and cell functions. It has been linked to tumorigenesis, development and metastasis in colorectal cancer (CRC). Recently, the let-7 family has been identified as a tumor suppressor in different types of cancers. However, the function of the let-7 family in CRC metastasis has not been fully investigated. Here, we focused on analyzing the role of let-7g in CRC. The Cancer Genome Atlas (TCGA) genomic datasets of CRC and detailed data from a Taiwanese CRC cohort were applied to study the expression pattern of let-7g. In addition, in vitro as well as in vivo studies have been performed to uncover the effects of let-7g on CRC. We found that the expression of let-7g was significantly lower in CRC specimens. Our results further supported the inhibitory effects of let-7g on CRC cell migration, invasion and extracellular calcium influx through store-operated calcium channels. We report a critical role for let-7g in the pathogenesis of CRC and suggest let-7g as a potential therapeutic target for CRC treatment.

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Dysregulation of miRNA in chronic hepatitis B is associated with hepatocellular carcinoma risk after nucleos(t)ide analogue treatment

Cited by 19 publications

References 56 publications

miR-140-3p Knockdown Suppresses Cell Proliferation and Fibrogenesis in Hepatic Stellate Cells via PTEN-Mediated AKT/mTOR Signaling

miR-140-3p Knockdown Suppresses Cell Proliferation and Fibrogenesis in Hepatic Stellate Cells via PTEN-Mediated AKT/mTOR Signaling

Prognostic implications of decreased microRNA‑101‑3p expression in patients with non‑small cell lung cancer

Functional Effects of let-7g Expression in Colon Cancer Metastasis

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