Khanchuila Shingnaisui, PhD
Nominated From: University of Hawai’i
Research Site: Jawaharlal Nehru University
Research Area: Cancer
Primary Mentor: Verma Saguna, PhD
Research Project
Unraveling the role of Pin4, a Parvulin-type PPIase, in lung cancer: A mechanistic study
Lung cancer is the leading cause of cancer-related mortality worldwide, with KRAS mutations being the common mutations in many lung cancers. Despite the effort to improve conventional therapy, the mortality rate of lung cancer is still high due to increasing drug resistance, underscoring the urgent need for the development of effective molecular targets. Pin4, a parvulin-type peptidyl-prolyl cis/trans isomerase (PPIase), has been implicated in breast and prostate cancer progression. Notably, Pin4 is observed in exosomes derived from K-RAS collateral cancer cells, highlighting a potential link between Pin4 and the KRAS signaling pathway. However, there is no report on the involvement of Pin4 in lung cancer. Thus, we hypothesized that Pin4 may be involved in lung cancer progression by regulating the KRAS signaling pathway. In this study, we will utilize siRNA-mediated knockdown of Pin4 to investigate the role of Pin4 in cell growth, migration, and invasion, particularly in KRAS G12C mutant cells, and compare the results with those from non-mutant cell lines. Furthermore, to evaluate the potential mediator of Pin4 in the malignant behavior of lung cancer, we will analyze the association of Pin4 with KRAS signaling pathways. This study will provide the mechanistic insight into the role of Pin4 in lung cancer development and progression through the KRAS-driven pathway. Therefore, by characterizing Pin4 as a novel regulator of oncogenic pathways and tumor progression, this study aims to establish Pin4 as a potential therapeutic target for cancer treatment. This proposed study may also open new opportunities for developing therapeutic anti-cancer drugs to improve treatment outcomes and the quality of life for cancer patients.
Research Significance
Investigating the mechanistic role of Pin4 using siRNA-mediated knockdown in tumor growth, migration, and invasion in lung cancer with KRAS mutation will establish whether Pin4 functions as a novel regulator of oncogenic pathways in lung cancer. The outcome of this study has the potential to make cutting-edge advances in cancer therapy. Characterizing Pin4 as a novel therapeutic target could pave the way towards inventing a PPIase-based anti-cancer drug therapy for combating drug resistance and poor prognosis in lung cancer treatment. Furthermore, this outcome has broader implications beyond lung cancer, making a significant contribution towards innovative approaches across multiple cancers. Ultimately, this work will address the current need to improve treatment outcomes, management, and enhance the quality of life for cancer patients worldwide.
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