Mir-33 regulates cell proliferation and cell cycle progression

Cirera‐Salinas, Daniel; Pauta, Montse; Allen, Ryan M.; Salerno, Alessandro G.; Ramírez, Cristina M.; Chamorro-Jorganes, Aránzazu; Wanschel, Amarylis; Lasunción, Miguel A.; Morales-Ruíz, Manuel; Suárez, Yajaira; Baldán, Ángel; Esplugues, Enric; Fernández‐Hernando, Carlos

doi:10.4161/cc.11.5.19421

Cited by 156 publications

(114 citation statements)

References 43 publications

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“…It is suggested that miR-33 may function as a tumor-associated molecule, as miR-33b can inhibit cell growth and induce apoptosis through suppressing the activity of WNT/β-catenin signaling in lung adenocarcinoma cells (40), and also inhibit the proliferation and migration of osteosarcoma cells by targeting hypoxia-inducible factor-1α (41). With further in-depth study of miR-33a, it was identified that mir-33a can also affect cell proliferation and cell cycle progression in tumors by regulating cyclin-dependent kinase 5, cyclin D1 and Pim-1 (42,43), inhibit bone metastasis by targeting parathyroid hormone-related protein (19), and inhibit cancer cell growth, invasion and metastasis by regulating the expression of high mobility group AT-hook 2 (44) and β-catenin (45). However, to the best of our knowledge, no report previously existed regarding the role of miR-33a in HCC.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-33a downregulation is associated with tumorigenesis and poor prognosis in patients with hepatocellular carcinoma

Xie

Cong

Zhong³

et al. 2018

Oncol Lett

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Abstract. In order to examine the prognostic significance of miR-33a in patients with hepatocellular carcinoma (HCC), total RNA was extracted from 149 HCC biopsies, 36 of which were paired with para-carcinoma tissues, and miR-33a expression was measured by reverse transcription-quantitative polymerase chain reaction. The results demonstrated that miR-33a expression was decreased in HCC biopsies compared with normal liver tissue samples. It was also demonstrated that miR-33a expression was significantly associated with tumor foci number. Furthermore, overall and progression-free survival time was decreased in patients expressing low miR-33a with multiple tumor foci. Taken together, the low expression of miR-33a may be a potential risk factor for HCC. IntroductionHepatocellular carcinoma (HCC) is the sixth most prevalent cancer worldwide, and is associated with an extremely poor prognosis (1-3). A principal reason for the high mortality of this disease is the failure of early diagnosis for patients with HCC and the lack of effective therapies for patients with HCC in advanced stages. Despite a number of advances made in therapeutic strategies and surgery, the overall prognosis for patients with HCC remains poor due to the high rate of metastasis and recurrence (4-6). Hence, the characterization of the molecular mechanisms in HCC is urgently required to allow the development of novel treatment methods for patients with HCC.MicroRNAs (miRNAs/miRs) are small non-coding RNAs (21-23 nucleotides) that are transcribed as precursors in the nucleus and are subsequently processed into mature miRNAs in the cytoplasm. Mature miRNAs primarily function by sequence specific interactions with the 3'-untranslated regions of mRNAs, leading to the translational suppression or degradation of the mRNAs (7). An increasing number of studies have suggested that miRNAs serve an essential role as prognostic and predictive biomarkers in various types of cancer. For example, miR-1290 and miR-196b have been demonstrated to predict the chemotherapeutic response of patients with lung adenocarcinoma (8). miR-149, an anti-tumor miRNA, has been identified as dysregulated in a variety of types of cancer, including gastric (9), breast (10) and colorectal cancer (11,12).It is also reported that a number of are associated with HCC carcinogenesis, progression and metastasis, including miR-15b (13), miR-122 (14) and miR-29 (15). Furthermore, the low expression of miR-124 is significantly associated with a more aggressive phenotype and a poorer prognosis (16), whereas a high expression of miR-182 has been associated with intrahepatic metastasis and poor prognosis in HCC (17). However, the mechanism of these miRNAs and their regulatory networks in HCC remain elusive, and a number of miRNAs that are associated with HCC have yet to be considered.miR-33a was originally demonstrated to regulate lipid and cholesterol metabolism (18), and is an intronic miRNA located within the sequence of the sterol regulatory element binding protein 2 (SREBP-2) gene. miR-33a ...

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Section: Discussionmentioning

confidence: 99%

MicroRNA-33a downregulation is associated with tumorigenesis and poor prognosis in patients with hepatocellular carcinoma

Xie

Cong

Zhong³

et al. 2018

Oncol Lett

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“…Many of the bovine miRNAs differentially expressed in large atretic follicles are reportedly involved in regulating the proliferation and survival of different cell types (miR-483, miR-150, miR-21, miR-409a, miR-31, miR-34b, miR-33a; Yamakuchi et al 2008, Bertero et al 2011, Liu et al 2011, Brabletz 2012, Cirera-Salinas et al 2012, Weng et al 2012 as well as immune cell activation (miR-150, miR-21, miR-31; Xiao et al 2007, Xue et al 2013, Das et al 2014, which is consistent with an active role of these miRNAs in follicular fate decisions. The involvement of miR-21 in the promotion of cell survival is well established, including in mouse granulosa cells during ovulation (Carletti et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Characterization of microRNAs differentially expressed during bovine follicle development

Sontakke¹,

Mohammed²,

McNeilly³

et al. 2014

Reproduction

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Several different miRNAs have been proposed to regulate ovarian follicle function; however, very limited information exists on the spatiotemporal patterns of miRNA expression during follicle development. The objective of this study was to identify, using microarray, miRNA profiles associated with growth and regression of dominant-size follicles in the bovine monovular ovary and to characterize their spatiotemporal distribution during development. The follicles were collected from abattoir ovaries and classified as small (4-8 mm) or large (12-17 mm); the latter were further classified as healthy or atretic based on estradiol and CYP19A1 levels. Six pools of small follicles and individual large healthy (nZ6) and large atretic (nZ5) follicles were analyzed using Exiqon's miRCURY LNA microRNA Array 6th gen, followed by qPCR validation. A total of 17 and 57 sequences were differentially expressed (greater than or equal to twofold; P!0.05) between large healthy and each of small and large atretic follicles respectively. Bovine miRNAs confirmed to be upregulated in large healthy follicles relative to small follicles (bta-miR-144, bta-miR-202, bta-miR-451, bta-miR-652, and bta-miR-873) were further characterized. Three of these miRNAs (bta-miR-144, bta-miR-202, and bta-miR-873) were also downregulated in large atretic follicles relative to large healthy follicles. Within the follicle, these miRNAs were predominantly expressed in mural granulosa cells. Further, body-wide screening revealed that bta-miR-202, but not other miRNAs, was expressed exclusively in the gonads. Finally, a total of 1359 predicted targets of the five miRNAs enriched in large healthy follicles were identified, which mapped to signaling pathways involved in follicular cell proliferation, steroidogenesis, prevention of premature luteinization, and oocyte maturation.

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“…Recently, the roles of miRNAs in HCC have been investigated, with results indicating that the expression and/or function of miRNAs become aberrant in the pathogenesis of HCC (7). miR-33a is a member of the highly conserved miR-33 family and is an intronic miRNA located within the genes of sterol regulatory element-binding proteins (11,12), where it principally regulates the metabolism of cholesterol (13) and glucose (14). In addition to its functional roles in metabolism, miR-33a has been implicated in a number of human cancers.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-33a promotes cell proliferation and inhibits apoptosis by targeting PPARα in human hepatocellular carcinoma

Chang

Zhang

Xian

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. ) is dysregulated in a number of human cancers, where it functions as an oncogenic miRNA. However, the clinical significance of miR-33a and its underlying molecular pathways regarding the progression of hepatocellular carcinoma (HCC) are currently unknown. In the present study, it was observed that the level of miR-33a expression was significantly increased in HCC tissues, relative to adjacent non-tumor tissues. Increased miR-33a expression was significantly correlated with poor prognostic features of HCC, including larger tumor size, higher Edmondson-Steiner grading and higher tumor-node-metastasis tumor stage. Furthermore, high levels of miR-33a expression were associated with decreases in the 5-year overall survival rate and recurrence-free survival of patients with HCC. In addition, functional experiments indicated that overexpression of miR-33a led to increased proliferation and reduced apoptosis of the HCC cell line Huh7, while knockdown of miR-33a decreased proliferation and induced apoptosis in the HCC cell line HepG2. Furthermore, peroxisome proliferator activated receptor alpha (PPARα) was identified as a direct target of miR-33a in HCC. Upregulation of miR-33a was found to reduce the levels of PPARα expression in Huh7 cells, while inhibition of miR-33a lead to a downregulation in PPARα expression in HepG2 cells. Collectively, these results suggest that miR-33a regulates the proliferation and apoptosis of HCC cells, and is a potential prognostic marker of HCC.

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Mir-33 regulates cell proliferation and cell cycle progression

Cited by 156 publications

References 43 publications

MicroRNA-33a downregulation is associated with tumorigenesis and poor prognosis in patients with hepatocellular carcinoma

MicroRNA-33a downregulation is associated with tumorigenesis and poor prognosis in patients with hepatocellular carcinoma

Characterization of microRNAs differentially expressed during bovine follicle development

MicroRNA-33a promotes cell proliferation and inhibits apoptosis by targeting PPARα in human hepatocellular carcinoma

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