7q22.1

MIRN106B,mir-106b

Various cancers

Deregulated expression of miR-106b has been implicated in various tumor types. In connection, miR-106b is thought to play an important role in cell cycle progression by targeting CDKN1A (p21) and E2F1 which in turns increase the proliferation rate of cells.

Gastric cancer

In a microarray study of 20 gastric primary tumors, miR-106b was shown to be upregulated together with miR-25 and miR-93 (other members of miR-106b-25 cluster) (Petrocca et al., 2008). Moreover, in a study conducted with 60 gastric cancer patients and 60 matched controls, plasma expression level of 15 selected microRNAs were measured by quantitative RT-PCR and 3 plasma microRNAs miR-106b, miR-20a, and miR-221 were found to be significantly increased. Hence, these microRNAs were suggested as potential bio-markers for early detection of gastric cancer (Cai et al., 2013).

Esophageal adenocarcinoma

5 esophageal cultured cells, 68 esophageal tissues (24 Barretts esophagus, 22 esophageal adenocarcinoma and 22 normal epithelia) were analyzed by microarray to have a profile of differentially expressed miRNAs and miR-106b-25 cluster was shown to be upregulated in esophageal carcinoma (Kan et al., 2009).

Prostate cancer

In a microarray study conducted with 60 prostate tumors and 16 non-tumor prostate tissues, tumor samples were found to have higher levels of miR-106b-25 cluster compared to non-tumor tissues (Ambs et al., 2008).
Tumorigenic effects of miR-106b in prostate cancer was suggested to be exerted by targeting PTEN (phosphate and tensin homolog) - a tumor suppressor gene. PTEN inhibits the PI3K-Akt pathway which is a signal transduction pathway taking role in cell survival, proliferation, motility and angiogenesis (Poliseno et al., 2010).

Hepatocellular carcinoma

56 pairs of hepatocellular carcinoma (HCC) samples and corresponding non-tumor liver samples were analyzed and significant up-regulation of miR-106b was observed in tumor samples. Moreover in this study, decrease in the proliferation of two hepatoma-derived cell lines was shown after inhibiting miR-106b by an anti-miR-106b oligo. BCL2L11 (Bim) was identified as target of miR-106b and correlation between BCL2L11 (Bim) (pro-apoptotic gene) and miR-106b was shown in hepatocellular carcinoma. Bim expression was higher in tumors that have down regulated expression of miR-106b (Li et al., 2009). The same upregulated pattern of miR-106b was shown in the study of Shen et al. (2013), in which HCC cell lines and tissues were analyzed by quantitative RT-PCR in terms of miR-106b expression. It was depicted that miR-106b upregulation affected G1/S transition by upregulating cyclin D1 and downregulating adenomatous polyposis coli (APC) - an important tumor suppressor gene. APC was shown as a direct target of miR-106b in this study.

Hepatocellular carcinoma (HCC) and hepatitis B virus (HBV) infection

A genetic variant (SNP A>G) in the promoter region of miR-106b-25 cluster suggested to provide a protective effect against HBV chronic infection. However, the polymorphism was also predicted to cause increased risk for HCC by increasing expression of miR-106b-25 cluster (Liu et al., 2012).

Breast cancer

In a study conducted with 204 lymph node negative breast cancers, high expression of miR-106b was shown to be correlated with high proliferation and estrogen receptor positivity (Jonsdottir et al., 2012). The role of miR-106b-25 cluster in breast cancer was depicted with study of Smith and his colleagues. The relation between miR-106b-25, TGFβ and homeobox protein SIX1 (Six1) was studied. It was shown that miR-106b-25 cluster can target Smad-7 - a TGFβ inhibitor - and activate TGFβ pathway as a downstream effect of SIX1 overexpression. Hence, miR-106b-25 cluster overcomes TGFβ mediated growth suppression and also promote TGFβ pathway signaling in favor of tumorigenesis (Smith et al., 2012).
Loss of membranous E-cadherin is known as one of the hallmarks for epithelial-to-mesenchymal transition (EMT). miR-106b-25 cluster overexpressing breast cancer cells had decreased membrane bound E-cadherin, which was in agreement with EMT (Smith et al., 2012).

Laryngeal carcinoma

Inhibition of miR-106b by antisense oligonucleotides showed a decrease in proliferation of two laryngeal carcinoma cell lines and this inhibition resulted in G0/G1 arrest (Cai et al., 2011). Retinoblastoma protein (Rb), which is a tumor suppressor and has a role in G1/S transition, was shown as a direct target of miR-106b in laryngeal carcinoma.

Glioma

miR-106b levels were assessed in 71 glioma samples and overexpression was observed in the majority of samples by in situ hybridization (ISH) and real-time PCR. Moreover, expression of miR-106b was found to be positively correlated with the tumor grade. After the transfection of antisense oligonucleotides for miR-106b in three human glioma cell lines, a decrease in the proliferation of these cells was observed. RBL2 (retinoblastoma like-2) was also shown to be target of miR-106b and miR-106b promoted cell cycle progression by negatively regulating RBL2 (Zhang et al., 2013).

Alzheimers disease (AD)

miR-106b levels were shown to be reduced in sporadic AD patients. Important role of TGFβ pathway has been implicated in AD pathogenesis (Tesseur et al., 2006; Caraci et al., 2011) and direct regulation of TGFβ receptor 2 (TGFBR2) by miR-106b was revealed. Hence, potential role of miR-106b in AD pathogenesis via affecting TGFβ pathway was suggested (Wang et al., 2010).

Induced pluripotent stem cells (iPSC)

In iPSC, miR-106b-25 cluster is induced in early reprogramming phases and inhibition of this cluster reduces the reprogramming efficiency. miR-93 and miR-106b target TGFBR2 and CDKN1A (p21) which have already been linked to iPSC induction (Li et al., 2011).