MicroRNA-32 (miR-32) is upregulated in colorectal cancer (CRC) tissues; its overexpression leads to increased cell proliferation, migration and invasion, as well as reduced apoptosis of CRC cells, at least partly by inhibiting the target gene phosphatase and tensin homolog.
Interestingly, PTEN can also exert some biological functions independently of its catalytic activity.A feature of colorectal cancers is the relatively low incidence of PTEN mutation or deletion, whereas PTEN downregulation occurs in approximately one third of tumours.
Two main elements of the PI3K-Akt signaling pathway, phosphatase and tensin homolog deleted on chromosome 10 and B-cell lymphoma 2-associated agonist of cell death, were demonstrated to be downregulated in CRC.
Treatment with everolimus decreases MCL-1 in colorectal carcinomas and small cell lung cancer (SCLC) cells but not glioblastoma multiforme (GBM) cells with a PTEN mutational background.
We observed a negative correlation between PTEN and mir-26a expression in cell lines, human tissues, TCGA data, and tissues derived from the CRC mouse model.
Our findings show that SCD1 promotes metastasis of CRC cells through MUFA production and suppressing PTEN in response to glucose, which may be a novel mechanism for diabetes-induced CRC metastasis.
Our data demonstrated that suppression of miR-29a enhanced PTEN expression, inhibited cancer cell proliferation, facilitated apoptosis, and weakened drug resistance, which provides academic basis for the treatment of colorectal cancer.
Taken together, our results elucidate the role of the LINC00312-miR-21-PTEN axis in CRC cell proliferation and tumour progression and may lead to new lncRNA-based diagnostics or therapeutics for CRC.
Furthermore, DJ-1 overexpression in two colon cancer cell lines, HCT116 and SW480, activated protein kinase AKT and downregulated tumor suppressor PTEN, whereas DJ-1 knockdown upregulated PTEN expression and effectively suppressed CRC cell invasion and proliferation both in vitro and in vivo, revealing a mechanism underlying DJ-1 pro-oncogenic activity in CRC.
We have developed and validated for the diagnosis of inherited colorectal cancer (CRC) a massive parallel sequencing strategy based on: (i) fast capture of exonic and intronic sequences from ten genes involved in Mendelian forms of CRC (MLH1, MSH2, MSH6, PMS2, APC, MUTYH, STK11, SMAD4, BMPR1A and PTEN); (ii) sequencing on MiSeq and NextSeq 500 Illumina platforms; (iii) a bioinformatic pipeline that includes BWA-Picard-GATK (Broad Institute) and CASAVA (Illumina) in parallel for mapping and variant calling, Alamut Batch (Interactive BioSoftware) for annotation, CANOES for CNV detection and finally, chimeric reads analysis for the detection of other types of structural variants (SVs).
Conversely, PTEN protein expression was markedly lower in CRC compared with adjacent normal tissues. p‑4E‑BP1 protein upregulation tissues samples was consistent with PTEN downregulation in CRC samples. p‑4E‑BP1 overexpression was predominant in patients with metastasis to the regional lymph nodes.
Breast cancer patients with an identified germline PTEN mutation are at increased risk of endometrial, thyroid, renal, and colorectal cancers as well as a second breast cancer.
In this study, we analyzed the mechanisms by which lithium can modulate events related to colorectal cancer (CRC) progression and evaluated the role that survival signaling pathways such as PI3K/Akt and PTEN play in this context.