異種型核糖核蛋白M（hnRNPM）藉由選擇性剪接或啟動子取代方式而產生3種轉錄變異體，並產生3種蛋白質同種型。先前的研究指出hnRNPM會促進大腸直腸癌的癌化發展。雖然這些研究皆證明了hnRNPM會促使大腸直腸癌化提升，但並未對不同亞型做探討。因此，hnRNPM異種型在大腸直腸癌中的相對貢獻值得我們進行研究。我們藉由使用異構體特異性引子和hnRNPM抗體分別偵測hnRNPM異種型在各種大腸直腸癌細胞中mRNA和蛋白質的表現量。另外，藉由核質分離的實驗用於確定hnRNPM亞型的細胞定位。而結果顯示hnRNPM異種型mRNA和蛋白質的表現在大腸直腸癌細胞中表現量高於正常結腸細胞株CRL1790。另外，所有hnRNPM表現量主要位於細胞核中。接著，我們藉由MTS assay和傷口癒合試驗探討hnRNPM異種型細胞增殖和爬行能力。我們發現在hnRNPM受抑制細胞中亦會抑制細胞增殖和爬行能力。但是在將hnRNPM異種型回補後，我們發現亦能拯救細胞的增殖和爬行能力,其中特別是isoform a部分具有顯著的回補效應。總之，我們的研究提供了第一次進一步了解hnRNPM異種型在大腸直腸癌中的作用。

Heterogeneous nuclear ribonucleoprotein M (hnRNPM) has multiple transcript variants due to alternative splicing or alternative promoter events and resulted in 3 protein isoforms.Previous studies have shown that hnRNPM promotes cancer progress in colorectal carcinoma(CRC). Although these studies clearly demonstrated the role of hnRNPM in CRC tumorigenesis, the tumorigenic effect from different isoforms was not discussed. It is of interest to study the relative contribution of hnRNPM isoforms in colorectal carcinoma tumorigenesis. We applied isoform-specific primers and hnRNPM pan-antibody to detect the distribution of hnRNPM mRNA and protein isoforms in various CRC cell lines. Furthermore, fractionated cell lysates were used to determine the cellular localization of hnRNPM isoforms. The result showed the expression of hnRNPM isoforms in colorectal cancer cell lines are significantly higher than that of normal colon cell line CRL1790. In the meanwhile, all hnRNPM protein isoforms are more abundant in the nuclear than that in the cytosol. To examine the tumorigenic effect of hnRNPM isoforms, we performed cell proliferation and migration tests by using MTS and wound healing assays, respectively, in hnRNPM- knockdown cell lines. We found cell proliferation and migration were significantly inhibited under decreased level of hnRNPM, indicating the important role of hnRNPM on cell growth and mobility. Interestingly, transiently overexpress hnRNPM isoforms in hnRNPM- knockdown cell lines rescued cell proliferation and migrations. Among them, overexpression of hnRNPM a isoform showed the best rescue ability. Taken together, our study provides, for the first time, further insight to understand the effect of hnRNPM isoforms in colon cancer tumorigenesis.

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