• 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2020-03
  • 2020-07
  • 2020-08
  • Lung cancer causes irregular cell proliferation in the lung


    Lung cancer causes irregular cell proliferation in the lung through primary genetic or epigenetic modification [9]. Abnormal AMG-176 can form a tumor mass, requiring nutrients and oxygen though blood vessel formation, including angiogenesis [10]. These cells overcome anti-cancer therapy and express oncogenes or tumor suppressor genes [11]. Likewise, expression of oncogenes and tumor suppressor genes is negatively regulated by specific miRNAs. Among them, let-7 negatively regulates oncogenes such as RAS, MYC, HMGA2 [12] and is downregulated in non-small cell lung cancer (NSCLC) patients with a let-7 family chromosomal deficiency [13]. miR-9500 directly suppresses Akt1, which negatively regulates proliferation and metastasis in lung cancer [14]. On the other hand, the miR-17-92 cluster is overexpressed and modulates tumor formation in lung cancer [15]. miR-205 promotes cell proliferation through targeting PTEN and PHLPP2 in NSCLC [16]. These miRNAs are involved in AMG-176 tumorigenesis in human lung cancer. Apoptosis is the programmed cell death important for cell division and differentiation [17]. Dysregulation of apoptosis causes abnormal cell growth and various diseases [18]. Apoptosis is a multiple step process, with the expression of and interactions among pro-apoptotic proteins (including Bax, Bad, and Bak) or anti-apoptotic proteins (including Bcl-2, Bcl-xL, and Bcl-w) [17]. In cancer cells, pro-apoptotic proteins are significantly upregulated, whereas anti-apoptotic proteins are downregulated [18]. Additionally, specific miRNAs negatively regulate these genes [8]. miR-192 regulates cell proliferation and promotes apoptosis by targeting retinoblastoma 1 in lung cancer cells [19]. miR-409-3p directly regulates PHF10, inhibiting cell proliferation and increasing apoptosis in gastric cancer cells [20]. These miRNAs are involved in apoptosis and inhibit cell proliferation in cancer cells.
    Materials and methods
    Discussion In this study, we discovered and characterized a novel miRNA, hsa-miR-CHA1, in lung cancer cell lines. miR-CHA1 is transcribed in the intergenic region between FADS2 and BEST1 on chromosome 11q12.3. The miR-CHA1 modified mature form is generated from precursor miRNA by dicer dependent processing (Supplementary Fig. 3). FADS2 function is lost in various cancers [24]. BEST1 increased cell proliferation in colonic carcinoma cells [25]. These regions demonstrate copy number alteration in cervical cancer [26]. Additionally, one study described genomic instability that caused loss of function in NSCLC such as translocation, deletion or chromosome loss [27]. miR-CHA1 expression is downregulated in NSCLC cell lines and tissues because of transcription at the 11q12.3 locus and is associated with the repression of cancer development in NSCLC. Following the functional analysis of miR-CHA, we identified upregulated expression of target genes in A549 cell lines. For novel miRNAs, we could not use target prediction programs (Target Scan, miRanda or miRDB) because they did not provide information about target genes [14,21]. Despite the problems with using target prediction programs, we discovered miR-CHA1 target genes using manual methods [[28], [29], [30]]. Using a luciferase assay, miR-CHA1 was verified to regulate X-linked inhibitor of apoptosis (XIAP) expression. XIAP is a member of the inhibitor of apoptosis (IAP) family. The IAP family is composed of eight members: NAIP, cIAP1, cIAP2, XIAP, ILP-2, ML-IAP, Survivin and Apollon [18]. These proteins affect various cellular mechanisms, including apoptosis [31]. XIAP activation prevented caspase-3 and caspase-7 activation of apoptosis by binding these two factors [32]. XIAP suppressed apoptosis networks and upregulated expression in malignant tissues compared with normal tissues (Supplementary Fig. 4) [33]. XIAP regulation by miRNAs was already reported. miR-7 inhibited cell proliferation and promoted apoptosis in cervical cancer by targeting BCL2 and XIAP [34,35]. Loss-of-function of miR-24 occurs in cancer cells, whereas XIAP is overexpressed [36]. miR-519d suppressed cell proliferation in ovarian cancer by targeting XIAP [37]. miR-CHA1 directly regulated the XIAP network, suppressing cell proliferation and promoting apoptosis in A549 cell lines.