Dataset Information

FOSB?PCDHB13 Axis Disrupts the Microtubule Network in Non-Small Cell Lung Cancer.

ABSTRACT: Non-small cell lung cancer (NSCLC) is among the leading causes of human mortality. One reason for high rates of NSCLC mortality is that drug resistance is a major problem for both conventional chemotherapies and less-toxic targeted therapies. Thus, novel mechanistic insights into disease pathogenesis may benefit the development of urgently needed therapies. Here we show that FBJ murine osteosarcoma viral oncogene homolog B (FOSB) was induced by an antimicrobial peptide, tilapia piscidin-4 (TP4), through the dysregulation of mitochondrial Ca2+ homeostasis in NSCLC cells. Transcriptomic, chromatin immunoprecipitation quantitative PCR, and immunocytochemical studies reveal that protocadherin-?13 (PCDHB13) as a target of FOSB that was functionally associated with microtubule. Overexpression of either PCDHB13 or FOSB attenuated NSCLC growth and survival in vitro and in vivo. Importantly, downregulation of both FOSB and PCDHB13 was observed in NSCLC patients and was negatively correlated with pathological grade. These findings introduce the FOSB?PCDHB13 axis as a novel tumor suppressive pathway in NSCLC.

SUBMITTER: Ting CH

PROVIDER: S-EPMC6357195 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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FOSB⁻PCDHB13 Axis Disrupts the Microtubule Network in Non-Small Cell Lung Cancer.

Ting Chen-Hung CH Lee Kang-Yun KY Wu Sheng-Ming SM Feng Po-Hao PH Chan Yao-Fei YF Chen Yi-Chun YC Chen Jyh-Yih JY

Cancers 20190117 1

Non-small cell lung cancer (NSCLC) is among the leading causes of human mortality. One reason for high rates of NSCLC mortality is that drug resistance is a major problem for both conventional chemotherapies and less-toxic targeted therapies. Thus, novel mechanistic insights into disease pathogenesis may benefit the development of urgently needed therapies. Here we show that FBJ murine osteosarcoma viral oncogene homolog B (FOSB) was induced by an antimicrobial peptide, tilapia piscidin-4 (TP4), ...[more]

PMID: 30658436

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Project description:Long non-coding RNAs (lncRNAs) serve important regulatory roles in human tumors. The aim of the present study was to examine the role of ribonuclease P RNA component H1 (RPPH1) in non-small cell lung cancer (NSCLC). RPPH1 expression was assessed in datasets from The Cancer Genome Atlas, as well as lung cancer cell lines and patients with NSCLC. RPPH1 was significantly upregulated in NSCLC cell lines, compared with a normal lung epithelial cell line. Moreover, high RPPH1 expression was associated with poor overall survival and disease progression. RPPH1 was knocked down in A549 and H1299 cells using short hairpin (sh) RNA constructs, and the expressions of target genes and proteins were determined by reverse transcription-quantitative PCR and western blotting. Cell invasion potential was also determined using Transwell Matrigel assays. Compared with the negative control, RPPH1 silencing significantly reduced the number of invading cells, increased E-cadherin expression and reduced vimentin protein expression. Cell resistance to cisplatin/cis-diamminedichloridoplatinum (CDDP) was also evaluated using Cell Counting Kit-8 and colony formation assays. RPPH1 overexpression increased the resistance of A549 and H1299 cells to CDDP. Moreover, the potential interactions between RPPH1, microRNA (miR)-326 and Wnt family member 2B (WNT2B) were investigated using luciferase reporter assays and co-transfection experiments. MiR-326 expression was directly inhibited by RPPH1. In A549 cells co-transfected with shRPPH1 and miR-326 inhibitor, the invading cell number significantly increased compared with cells transfected with shRPPH1 alone. In addition, E-cadherin expression levels were reduced, and vimentin was upregulated. MiR-326 overexpression partially reduced the resistance of A549 cells to CDDP induced by RPPH1 overexpression. WNT2B expression was directly suppressed using miR-326. A549 cells co-transfected with a miR-326 mimic and a WNT2B overexpression vector demonstrated increased invasion potential, reduced E-cadherin and increased vimentin protein expression levels, compared with cells transfected with the mimic alone. miR-326 overexpression reduced CDDP resistance in A549 cells. However, co-transfection with WNT2B partially enhanced CDDP resistance, compared with the mimic alone. In conclusion, RPPH1 promoted NSCLC progression and lung cancer cell resistance to CDDP through miR-326 and WNT2B.

Dataset Information

FOSB?PCDHB13 Axis Disrupts the Microtubule Network in Non-Small Cell Lung Cancer.

Publications

FOSB⁻PCDHB13 Axis Disrupts the Microtubule Network in Non-Small Cell Lung Cancer.

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