The molecular mechanisms of CLNS1A-induced cell transformation in lung cancer cell line H1299

• Main Authors: Wang, Yi-Wun, 王怡文
• Other Authors: Yu, Chang-Tze
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/97014001863399523636

碩士 === 國立暨南國際大學 === 應用化學系 === 103 === Chloride channel nucleotide sensitive 1A (CLNS1A), a multifunctional protein, belongs to a member of volume-sensitive organic osmolyte/anion channel (VSOAC) and is a chloride channel controlling the outward flow of chloride ion. Moreover, CLNS1A is suggested as a component of methylosome with PRMT5 and MEP50, specifying the substrate selection of the protein methyltransferase complex. Importantly, the members of VASOC family have been pointed out to be engaged in several carcinogenesis processes such as cell proliferation, migration, invasiveness, angiogenesis, apoptosis and cell adhesion; however, our published works have shown that PRMT5 and MEP50 work as oncoproteins. Accordingly, it is logically anticipated that CLNS1A should have a role in cancer formation. To rapidly understand whether CLNS1A is involved in cancer development, we have screened the expression of CLNS1A in collected panels of lung cancer tissues by analyzing the level of protein. Overexpression of CLNS1A increases, while silence of CLNS1A decreases, cell migration, cell growth in cultured dishes and nude mice, and anchorage-independent growth in lung cancer cell lines, implying CLNS1A as an oncoprotein candidate. Mechanistic analyses show that inhibition of CLNS1A, or knockdown of PRMT5, attenuated the cell transforming activities of CLNS1A, indicating CLNS1A transforms cells via separated pathways. We observed CLNS1A promotes cell proliferation through chloride channel regulated; while CLNS1A stimulated cell migration and enhance anchorage-independent-growth via Chloride channel and PRMT5 modulated.