miR-10b對於肺癌細胞株的功能性角色

中文摘要肺癌是長在氣管、支氣管或是肺部實質組織的惡性腫瘤，目前是在全球發生率與日俱增的癌症之一，患者在胸腔的X光影像上常可見到白色局部實質病變影像。而確立診斷再依據病理切片以組織學型態分為小細胞癌以及非小細胞癌；而非小細胞癌又分為肺腺癌、鱗狀細胞癌以及大細胞癌，其中以肺腺癌在台灣最為常見。微小核酸MicroRNA (miRNA) 是非編碼的單股RNA，以後轉錄的方式調節特定基因的表達。MicroRNA已被證實可以影響癌細胞的形成，浸潤，轉移和對藥物的抗性。腫瘤抑制型和致癌型miRNA被發現在許多腫瘤，包括肺癌的發生與惡化中扮演很關鍵的角色，同時miRNA也被認為是針對癌症的新穎性治療方法與標的。過去的研究及前面的敘述得知，MicroRNA在肺癌的病程中扮演雙重角色，並且可影響癌細胞的轉移以及和化療藥物Cisplatin的交互作用。然而miR10b雖參與影響肺癌細胞的轉移的過程，但對Cisplatin的交互作用在肺癌中的影響角色仍不清楚，因此本論文的研究將著重於這一部分的探討。研究中，我們透過肺癌細胞株，以Western blot，Q-PCR，Invasion assay以及 Luciferase assay等實驗方法分別觀察不同的肺癌細胞株其miR-10b的表現，以及miR-10b對於肺癌細胞侵犯能力以及EMT現象的影響。再利用Cisplatin處理肺癌細胞株，觀察Cisplatin對於miR-10b引發反應的影響。研究結果顯示，在不同的肺癌細胞中之致癌型微小核酸 mir-10b的表現量明顯不同。miR-10b可促進肺癌細胞的侵犯能力，且可抑制如A549細胞株其相關細胞凋亡分子Bax以及抑癌分子p53的表現。而Cisplatin則可促進A549細胞的抑癌基因p53的表現，並抑制miR-10b所引發的抑癌基因抑制現象。顯示miR-10b在未來可能可作為肺癌治療的新標的。

關鍵字

肺癌

並列摘要

Abstract Lung cancer is a malignant lung tumor characterized by uncontrolled cell growth in tissues of trachea, bronchus and lung. Currently, lung cancer is one of cancers with high incidence. In chest X-ray study, images of white localized parenchymal lesions were seen in patients with lung cancer. According to the pathological biopsy test, lung cancer is classified into two categories: small cell carcinoma and non-small cell carcinoma. Furthermore, non-small cell carcinoma is classified into lung adenocarcinoma, squamous cell carcinoma and large cell carcinoma. Lung adenocarcinoma is the most common lung cancer in Taiwan. Micro-Nucleic acid microRNAs (miRNAs) are encoded single strand RNAs that post-transcriptionally regulate gene expression. MicroRNA has been shown to affect the formation, infiltration, metastasis and resistance of chemical therapy of cancer cells. Tumor suppressor and carcinogenic miRNA have been found to play a key role in many cancers, including lung cancer, and miRNA is also considered novel therapies and targets for cancer. Recent studies indicated that miRNAs play dual role in the course of lung cancer. Furthermore, miRNAs affect the metastasis of cancer cells and the interaction with chemotherapeutic drugs such as Cisplatin. However, while miR-10b is involved in the migration of lung cancer cells, but the functional role of miR-10b in lung cancer and Cisplatin interaction remains unclear. In this study, the functional role of miR-10b in lung cancer and chemotherapy of lung cancer were examined. Western blot, Q-PCR, invasion assay and Luciferase assay were utilized to observe the miR-10b manifestations of different lung cancer cell lines and the effects of miR-10b on lung cancer cell invasion and EMT, the effect of cisplatin on miR-10b induced reaction was observed. Our results showed that the expression of carcinogenic miR-10b in different lung cancer cells was significantly different. miR-10b promoted the invasion ability of lung cancer cells, and inhibitd the expression of apoptosis molecule Bax and tumor suppressor molecule p53. Cisplatin the expression of tumor suppressor gene p53 in A549 cells and abolished the inhibition of tumor suppressor gene induced by miR-10b. In addition, inhibition of miR-10b could improve the effect of cisplatin therapy. Conclusion: miR-10b may be one of the potential targets in treatment of lung cancer.