Upregulated miR-9-3p Promotes Cell Growth and Inhibits Apoptosis in Medullary Thyroid Carcinoma by Targeting BLCAP

Abstract

Medullary thyroid carcinoma (MTC) is a neuroendocrine cancer derived from parafollicular C cells in the thyroid gland. It has great interest as a research focus because of its unusual genetic, clinical, and prognostic characteristics. However, the pathogenesis in MTC is not completely clear. We investigated the role of miR-9-3p and bladder cancer-associated protein (BLCAP) in MTC TT cells. First, miR-9-3p expression was upregulated in human MTC tissues and TT cells and compared to the control by RT-PCR. Flow cytometric analysis indicated that the cell cycle progression in TT cells was significantly inhibited by the miR-9-3p inhibitor but was increased by the miR-9-3p mimic. On the contrary, the apoptosis of TT cells was significantly increased by the miR-9-3p inhibitor and suppressed by the miR-9-3p mimic. A similar change pattern was observed in the expression of apoptosis-regulated protein caspase 3 induced by the miR-9-3p mimic or inhibitor in TT cells. We then identified that BLCAP is a target of miR-9-3p by bioinformatic prediction and luciferase reporter assay. The expression of BLCAP was also significantly downregulated by the miR-9-3p mimic while being upregulated by the miR-9-3p inhibitor in TT cells. Furthermore, we confirmed that the inhibited apoptosis of TT cells induced by the miR-9-3p mimic was enhanced by BLCAP overexpression. The levels of apoptosis were strongly decreased by BLCAP silencing in TT cells, which were not further influenced by the miR-9-3p inhibitor. In summary, upregulated miR-9-3p has a positive role in human MTC progression by regulating the growth and apoptosis of cancer cells via targeting BLCAP. This might represent a possible diagnosis or therapeutic target for MTC.

Candidate diagnostic miRNAs that can detect cancer in prostate biopsy

“…Many miRNAs identified as dysregulated in the present study have also been reported as altered in other cancer types, including breast cancer (miR‐374b‐5p, miR‐429, miR‐200b‐5p, miR‐200b‐3p, miR‐187‐3p, miR‐196a‐5p, miR‐183‐5p, miR‐21‐5p, and miR‐182‐5p); gastric cancer (miR‐374b‐5p, miR‐200c‐3p, miR‐18b‐5p, miR‐196a‐5p, miR‐21‐5p, and miR‐20a‐3p); ovarian cancer (miR‐141‐5p, miR‐182‐5p, miR‐483‐3p, and miR‐200c‐3p); hepatocellular carcinoma (miR‐135a‐5p, miR‐187‐3p, miR‐148a‐5p, miR‐200a‐3p, and miR‐9‐3p); colorectal cancer (miR‐9‐3p, miR‐135a‐5p, miR‐200c‐3p, miR‐200b‐3p, and miR‐182‐5p); thyroid cancer (miR‐7‐5p and miR‐9‐3p); lung cancer (miR‐200b‐5p, miR‐200b‐3p, miR‐9‐5p, miR‐200a‐3p, and miR‐21‐5p); pancreatic cancer (miR‐200b‐3p, miR‐483‐3p, and miR‐183‐5p); chronic lymphocytic leukemia (miR‐4521, miR‐7‐5p, and miR‐182‐5p); Hodgkin lymphoma (miR‐876‐5p); cervical cancer (miR‐429); head and neck squamous cell carcinoma (miR‐200b‐5p); and bladder cancer (miR‐148a‐3p) …”

Long non-coding RNA MALAT1 regulates BLCAP mRNA expression through binding to miR-339-5p and promotes poor prognosis in breast cancer

“…Furthermore, among target genes of miR-339-5p, as is shown in Figure 4B,C, BLCAP transcript level was significantly correlated with MALAT1 mRNA level and expression alterations of MALAT1, miR-339-5p and BLCAP in breast carcinoma were demonstrated from TCGA at cBioportal. In addition, it has been reported that BLCAP can be regulated by miR-9-3p to promote cell growth and inhibit apoptosis in medullary thyroid carcinoma [14], and there was only one potential complementary site for miR-339-5p in the 3′UTR of BLCAP mRNA. Therefore, we focused on BLCAP as the primary candidate.…”

MicroRNA-141-5p Acts as a Tumor Suppressor via Targeting RAB32 in Chronic Myeloid Leukemia

“…MiRNAs are involved in many biological processes, including cell proliferation, differentiation, and apoptosis, via the targeting of gene mRNA 3′UTR. Abnormal expression of certain miRNAs was observed in some cancers compared to normal tissues, such as endometrial carcinoma (Bao et al, 2013), breast cancer (Rhodes et al, 2015), ovarian cancer (Vilming Elgaaen et al, 2014), gastric cancer (Li et al, 2015), hepatocellular carcinoma (Yao et al, 2016), Hodgkin's lymphoma (Paydas et al, 2016), thyroid cancer (Chen et al, 2017), acute promyelocytic leukemia (Garzon et al, 2007), bladder cancer (Wang et al, 2016), and chronic lymphoblastic leukemia (Calin et al, 2005). Various miRNAs may act as oncogenes or tumor suppressor genes according to their roles in tumorigenesis (Boufraqech, Klubo-Gwiezdzinska, & Kebebew, 2016).…”