Mitogen-activated protein kinases (MAPKs) are the main regulators of cellular proliferation, growth, and survival in physiological or pathological conditions. Aberrant MAPK signaling plays a pivotal role in carcinogenesis, which leads to development and progression of human cancer. Dual-specificity phosphatase 6 (DUSP6), a member of the MAPK phosphatase family, interacts with specifically targeted extracellular signal-regulated kinase 1/2 via negative feedback regulation in the MAPK pathway of mammalian cells. This phosphatase functions in a dual manner, pro-oncogenic or tumor-suppressive, depending on the type of cancer. To date, the tumor-suppressive role of DUSP6 has been demonstrated in pancreatic cancer, non-small cell lung cancer, esophageal squamous cell and nasopharyngeal carcinoma, and ovarian cancer. Its pro-oncogenic role has been observed in human glioblastoma, thyroid carcinoma, breast cancer, and acute myeloid carcinoma. Both roles of DUSP6 have been documented in malignant melanoma depending on the histological subtype of the cancer. Loss- or gain-of-function effects of DUSP6 in these cancers highlights the significance of this phosphatase in carcinogenesis. Development of methods that use the DUSP6 gene as a therapeutic target for cancer treatment or as a prognostic factor for diagnosis and evaluation of cancer treatment outcome has great potential. This review focuses on molecular characteristics of the DUSP6 gene and its role in cancers in the purview of development, progression, and cancer treatment outcome.

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BACKGROUND: Molecular alterations of microRNA130a (miR130a) are observed in many types of cancers, including non-small cell lung cancer (NSCLC). However, the role of miR130a in NSCLC has been poorly studied.METHODS: In this study, clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 was utilised to knockdown miR130a. The gRNA was designed to target the stem loop, 3’ and 5’ sites of miR130a and stably expressed in A549 cells. Post-treatment, mature levels of miR130a-3p and 5p were quantified, and proliferation and migration assays were conducted.RESULTS: Result showed significant suppression of miR130a-3p and -5p by two and three-fold respectively, when the CRISPR/Cas9 targeted at the 3’ site and stem loop of the miR130a gene. Suppression of miR130a-3p significantly increased the growth and migration of A549 cells, but no significant changes were observed in cells with suppressed expression of miR130a-5p.CONCLUSION: Our encouraging results highlight that the suppression of the miR130a is achievable using CRISPR/Cas9, and suppression of the miR-130a-3p could play an important role in the regulation of NSCLC.KEYWORDS: miR130a, CRISPR-Cas9, non-small cell lung cancer